To observe the effect and mechanism of Jianpi Qushi Prescription(JPQS) on blood lipids，gastrointestinal function and water metabolism of hyperlipidemic rats with spleen deficiency and dampness.Methods:A total of 56 SD rats were randomly divided into blank group(n=8) and modeling group(n=48).A hyperlipidemic rat model with spleen deficiency and dampness was replicated by overfatigue+irregular diet+high-fat feeding.After 4 weeks of modeling，the modeling group was randomly divided into 6 groups according to total cholesterol(TC) level：model group，Xuezhikang group，Shenling Baizhu Granules group，and JPQS low-，medium-and high-dose groups，with 8 in each group.After grouping，drugs were administered by gavage at a dose of 1 mL/100 g.The blank group and the model group were given normal saline，while the other groups were given corresponding drugs for 6 consecutive weeks.Four blood lipid indexes[TC，triglycerides(TG)，low-density lipoprotein cholesterol(LDL-Ch)，high-density lipoprotein cholesterol(HDL-Ch)]，gastrointestinal hormones[motilin(MTL)，gastrin(GAS)，vasoactive intestinal peptide(VIP)]，water regulation hormones[aldosterone(ALD)，anti-diuretic hormone(ADH)，atrial natriuretic hormone(ANP)]，albumin(ALB) and total protein(TP) were detected.Hematoxylin-eosin(HE) staining was used to observe the morphology of gastric and colonic tissues.Immunofluorescence assay was performed to detect the expression position and level of aquaporin 3(AQP3) in colon and AQP4 in stomach，and Western blot was performed to detect the expression level of Occludin in colonic and gastric tissues.Results:Compared with the blank group，the model group had increased serum levels of TC，TG，and LDL-Ch(P<0.001)，VIP(P<0.001) and ALD and ADH(P<0.05，P<0.001)，and decreased serum levels of HDL-Ch(P<0.05)，MTL and GAS(P<0.001，P<0.01)，ANP(P<0.001) and TP and ALB(P<0.001，P<0.05).Additionally，colon villi and gastric mucosa were shed in large amounts in the model group，with reduced fluorescence intensity of AQP3 in colon，enhanced fluorescence expression of AQP4 in stomach，and down-regulated expression of Occludin in colon and gastric tissues.Compared with the conditions in the model group，the serum levels of TC，TG and LDL-Ch of rats in administration groups presented a downward trend，while the HDL-C level was elevated; MTL and GAS were significantly up-regulated，while VIP was significantly reduced; a decrease was found in ALD and ADH，while a remarkable increase was found in ANP; the morphological structure of colonic and gastric tissues was improved，with enhanced fluorescence expression of AQP3 in colon，weakened fluorescence intensity of AQP4 in stomach and elevated expression of Occludin in colonic and gastric tissues.Conclusion:JPQS reduces the blood lipids of hyperlipidemic rats with spleen deficiency and dampness and shows the effect of invigorating spleen and removing dampness.The mechanism may be regulating the expressions of Occludin，AQP3 and AQP4 to protect the structural integrity of tight junctions and promote gastrointestinal digestion and absorption，thereby improving the water metabolism disorders.