Aim To observe the influence of Huayuqutan recipe on the metabolism of cholesterol in apolipoprotein E gene knockout （ApoE^－/－） mice, so as to illuminate the role and mechanism of Huayuqutan recipe on atherosclerosis. Methods Ten C57BL/6/J mice were used as blank group. Thirty ApoE^－/－ mice were randomly divided into model group, Huayuqutan recipe group and simvastatin group. The levels of serum lipid were tested by biochemical methods. HE and oil red staining method were used to observe the aortic wall injury of ApoE^－/－ mice atherosclerotic mice.RT-PCR and Western blot methods were used to test the changes of expression of low-density lipoprotein receptor （LDLR）, lecithin-cholesterol acyl transferase （LCAT） in liver and CD36 in aortic wall. The expression of CD36 in macrophages was detected by flow cytometer. Results Compared with the blank group, the serum triglyceride （TG）, total cholesterol （TC） and low-density lipoprotein cholesterol （LDLC） levels and the expression of CD36 in aortic wall and macrophages were significantly increased while high-density lipoprotein cholesterol （HDLC） level and expression of LDLR, LCAT in liver were significantly decreased in the model group. In Huayuqutan recipe group and simvastatin group, the serum con tent of TG, TC and LDLC were lower and HDLC was higher compared with the model group. At the same time, the expression of LDLR, LCAT in liver were up-regulated and CD36 in aortic wall as well as macrophages was obviously down-regulated. Conclusion Huayuqutan recipe could inhibit the formation of the atherosclerotic plaques, which might be related to the regulation of blood lipid, the expression of LDLR, LCAT as well as CD36.