Objective To explore the effects of the Chinese medicine, modified Erchen decoction, on the serum lipid spectrum of ApoE^-/- mice, and to explore its possible anti-atherosclerotic mechanism. Methods Forty-four male 7-8-week old ApoE^-/- mice were used in this experiment. ApoE^-/- mouse models of atherosclerosis were generated by high-cholesterol diet for 4 weeks. And then, they were given simvastatin or modified Erchen decoction by gavage. The body weight of mice was recorded every week, The mice were sacrificed after treated with the drugs for 8 weeks continuously, and the plasma lipid was determined by enzymatic method. The aortic valves and arches were stained with oil red O to depict atherosclerotic plaques and liver structural changes of the mice were examined by pathology. Results Modified Erchen decoction lowered plasma lipid(including TCHOL and LDL-C)significantly (P<0.01). The body weight was increased in the mice of all groups, but it was more pronounced in the mice of model group than in the blank and modified Erchen decoction groups. The serum CHOL and LDL-C levels were significantly lowered in the modified Erchen decoction group (P<0.01). The area of atherosclerotic plaques in the aortic wall was significantly reduced in the mice of modified Erchen decoction group as shown by oil red O staining. The pathological changes of hepatocytes were less severe and the structure of hepatic lobules was better preserved in the mice of modified Erchen decoction group. Conclusions The Chinese medicin modified Erchen decoction can effectively reduce serum lipids, regulate lipid metabolism, and ameliorate the process of atherosclerosis in ApoE^-/- mice.