To investigate the effects of Congrong Shujing Granules on the expression of DJ-1 protein and the phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) signaling pathway in the hippocampus of Parkinson's disease(PD) model mice，and to explore the potential mechanisms underlying its therapeutic effects on PD.Methods:A total of 58 C57BL/6J mice were randomly divided into the blank control group(n=10) and the modeling group(n=48) according to a random number table.The PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)，and the successful model mice were further divided into the model group，low，medium，and high-dose Congrong Shujing Granules groups(n=11 in each group).After modeling，mice in the low，medium，and high-dose Congrong Shujing Granules groups received granule solutions at respective doses(186,371，and 742 mg/mL) by gavage at 0.01 mL/g for 14 days.The blank control group and model group received the same volume of saline，once daily for 14 days.Samples were collected 14 days after drug administration.Behavioral changes were observed through suspension and climbing tests before drug treatment and on day 7 and day 14 after drug treatment.Immunohistochemical analysis was used to detect TH-positive cells in the substantia nigra and DJ-1-positive cells in the hippocampus.Western blot was performed to assess the protein expression of DJ-1，AKT，PI3K，P-AKT，and P-PI3K in the hippocampus，and qPCR was employed to detected the mRNA levels of DJ-1，PI3K，and AKT in the hippocampus.Results:After modeling and on days 7 and 14 after treatment，the suspension test scores in the model group were significantly lower than those in the blank control group(P<0.05).On day 14，the suspension test scores of the Congrong Shujing Granules groups were higher than those in the model group(P<0.05).Before drug treatment and on the 7th day after drug treatment，the suspension test scores of all modeling groups were lower than those of the blank control group(P<0.05)，with no significant differences among the modeling groups.On the 14th day after drug treatment，there were no significant differences in suspension test scores between the medium-/high-dose groups with blank control group and low-dose group(P>0.05).However，compared to the model group，the suspension test scores were higher in the medium-/high-dose groups(P<0.05).The low-dose group had lower suspension test scores than the blank control group(P<0.05)，but the difference was not statistically significant compared to the model group(P>0.05).Compared to the blank control group，the model group had higher climbing test scores(P<0.05).On the 14th day after administration，the high-dose group had lower climbing test scores than the model group(P<0.05).Before administration，all modeling groups had higher climbing test scores than the blank control group(P<0.05)，with no significant differences among the modeling groups.On the 7th day after administration，the climbing test scores of the high-dose group showed no significant differences compared to the blank control group，low-dose group，and medium-dose group(P>0.05)，but were lower than those of the model group(P<0.05).The low-dose and medium-dose groups had higher climbing test scores than the blank control group(P<0.05)，but showed no significant differences compared to the model group and high-dose group(P>0.05).On the 14th day after administration，the high-dose group showed no significant differences compared to the blank control group(P>0.05)，but had lower climbing test scores than the model group，low-dose group，and medium-dose group(P<0.05).The low-dose and medium-dose groups had higher climbing test scores than the blank control group and high-dose group(P<0.05)，but showed no significant differences compared to the model group(P>0.05).Compared to the blank control group，the model group had a lower percentage of TH-positive cell area in the substantia nigra(P<0.05).Compared to the model group，the low-，medium-，and high-dose groups of Congrong Shujing Granules had higher percentages of TH-positive cell areas in the substantia nigra(P<0.05)，with the medium-and high-dose groups showing a higher percentage than the low-dose group(P<0.05).Compared to the blank control group，the model group had a lower percentage of DJ-1-positive cell area in the hippocampus(P<0.05).Compared to the model group，the low-，medium-，and high-dose groups of Congrong Shujing Granules had higher percentages of DJ-1-positive cell areas in the hippocampus(P<0.05)，and the percentage increased with increasing doses(P<0.05).Compared to the blank control group，the model group had lower relative DJ-1 mRNA expression(P<0.05).Compared to the model group，the low-，medium-，and high-dose groups of Congrong Shujing Granules had higher relative DJ-1 mRNA expression(P<0.05).There were no significant differences in the relative expression levels of AKT and PI3K mRNA among the groups(P>0.05).Conclusion:Congrong Shujing Granules may alleviate the behavioral symptoms of PD in mice by upregulating the mRNA and protein expression of DJ-1，promoting the phosphorylation of AKT and PI3K，activating the PI3K/AKT signaling pathway，and mitigating oxidative stress.