To explore the mechanism by which Yisui Jiedu Formula regulates synaptic plasticity in the hippocampus of vascular dementia(VD) rats through the Sonic Hedgehog(Shh) signaling pathway.Methods:Specific pathogen-free(SPF) male Sprague-Dawley(SD) rats were randomly assigned to the sham surgery group，model group，positive control group，and Yisui Jiedu Formula group according to the random number table method，with 10 rats in each group.Except for the sham surgery group，the other three groups were subjected to the 2-vessel occlusion(2-VO) method to establish the VD rat model.In the sham surgery group，only the common carotid arteries were cannulated without ligation.On the second day after modeling，rats in the positive control group were gavaged with 5.2 ×10-4 g/kg donepezil hydrochloride solution，rats in the Yisui Jiedu Formula group were gavaged with 11.11 g/kg of Yisui Jiedu Formula，and rats in the sham surgery and model groups were gavaged with an equal volume of physiological saline，once daily for 4 consecutive weeks.Behavioral tests were conducted using the Morris water maze.Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were used to observe the hippocampal morphology and synaptic ultrastructure in the CA1 region.Golgi staining was performed to assess the dendritic and dendritic spine morphology of pyramidal neurons in the hippocampal CA1 region.Real-time quantitative PCR(qPCR) was used to measure the mRNA expression levels of Shh，Smoothened(Smo)，and Gli1 in the hippocampus.Western blot was performed to detect the protein expression of synaptophysin(SYN)，Shh，Patched1(Ptch1)，Smo，and Gli1 in the hippocampus.Results:Compared to the sham surgery group，the model group showed longer escape latency and fewer platform crossings on day 4 of the Morris water maze test(P<0.01).Compared to the model group，the positive control and Yisui Jiedu Formula groups had shorter escape latency and more platform crossings on day 4(P<0.01).Compared to the model group，the positive control and Yisui Jiedu Formula groups showed less hippocampal tissue damage; the hippocampal synaptic structure was clearer，synaptic vesicle numbers were increased，and they were more densely distributed with better continuity of the pre-and post-synaptic membranes.Neurons in the hippocampal CA1 region showed more regular morphology，with increased dendritic branching and dendritic spines.Compared to the sham surgery group，the model group had lower mRNA expression levels of Shh，Smo，and Gli1 in the hippocampus(P<0.01).Compared to the model group，the positive control and Yisui Jiedu Formula groups had higher mRNA expression levels of Shh，Smo，and Gli1(P<0.05).Compared to the sham surgery group，the model group had lower protein expression of SYN，Shh，Ptch1，Smo，and Gli1 in the hippocampus(P<0.05).Compared to the model group，the positive control group had higher protein expression of Ptch1，Smo，and Gli1 in the hippocampus(P<0.05)，with SYN and Shh protein expression showing an increasing trend，but the difference was not statistically significant(P>0.05).The Yisui Jiedu Formula group showed higher protein expression of SYN，Shh，Ptch1，Smo，and Gli1 in the hippocampus(P<0.05).Conclusion:Yisui Jiedu Formula can significantly improve the learning and memory ability of VD rats.Its mechanism may be related to the activation of the Shh signaling pathway，repair of hippocampal neuron and synaptic ultrastructure damage，and promotion and regulation of synaptic plasticity.