Abstract: OBJECTIVE To explore the effect and mechanism of Zexieyin on the degree of artery lumen lesion and blood lipid level in ApoE^-/- mice model of atherosclerosis. METHODS Male ApoE^-/- mice were randomly divided into four groups: the high-fat diet group (HFD)， the low-dose ZXY group (LZXY)， the high-dose ZXY group (HZXY) and the atorvastatin group (ATO) as positive control group. All the above groups were fed a high-fat diet. Another blank control group (Con) was administrated only a normal diet. The levels of the serum total cholesterol (TC)， triglyceride (TG)， low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) were measured. The lesions of aortic arch root were observed by Oil Red O staining. Western blot was used to detect the expression levels of Liver X receptor (LXR) α， cholesterol 7 alpha-hydroxylase A1 (CYP7A1)， ATP-binding cassettes (ABC) G5 and ABCG8 in the liver， and LXR α， Niemann-pick C1-like 1 (NPC1L1)， sterol regulatory element binding protein (SREBP-2)， ABCG5 and ABCG8 in the small intestine. RESULTS The results showed that compared with the high-fat diet group， ZXY could significantly improve the blood lipid level and attenuate the atherosclerotic lesions in a dose-dependent manner. In the liver of mice， the expression levels of LXR-α， CYP7A1， ABCG5 and ABCG8 were significantly increased by ZXY. In the small intestine of mice， ZXY increased the expression levels of LXR-α， ABCG5 and ABCG8， and inhibited the expression levels of NPC1L1 and SREBP2. CONCLUSION ZXY can effectively inhibit the progression of AS and alleviate the blood lipid level， and its mechanism might be related to the inhibition of cholesterol absorption and the promotion of cholesterol excretion， which indicates that ZXY has potential value for prevention and treatment of AS.