OBJECTIVE： To observe the effects of Compound dongchong xiacao oral liquid on atherosclerosis （AS） in ApoE knock-out （ApoE-/-） mice， and to investigate its mechanism. METHODS： Totally of 45 male ApoE-/- mice were randomly divided into model group （normal saline）， positive group （atorvastatin， 5 mg/kg） and Compound dongchong xiacao oral liquid low-dose， medium-dose and high-dose groups（0.4， 1.2， 3.6 g/kg，by crude drug）， with 9 mice in each group. Another 9 male C57BL/6J mice were included in blank control group （normal saline）. Except blank control group was given common diet， other groups were given high lipid diet to induce AS model and given relevant medicine intragastrically once a day， for consecutive 8 weeks. After last medication， serum was isolated， and the levels of TC， TG， LDL-C and HDL-C were determined. Thoracic aorta and aortic sinus were separated and then stained with oil red O. The ratio of thoracic aortic plaque area （i.e. the ratio of thoracic aortic plaque area to total thoracic aorta area） and the ratio of aortic sinus lipid lesion area （i.e. the ratio of aortic sinus lipid deposition to total area of aortic sinus lumen） were determined. The expression of aortic sinus macrophage （i.e. the ratio of positive expression area of macrophage in plaque area） was determined by immunohistochemical method. RESULTS： Compared with blank control group， the serum levels of TC， TG and LDL-C were increased significantly in model group， while the level of HDL-C was decreased significantly （P＜0.01）. There were obvious plaque in thoracic aorta and obvious increase of sinus lipid deposition in aortic sinus； the ratio of aortic plaque area and the ratio of aortic sinus lipid lesion area were all increased significantly （P＜0.01）. The positive expression of aortic sinus macrophage was increased significantly， and its amount was also increased significantly （P＜0.01）. Compared with model group， the serum levels of TC， TG and LDL-C in administration groups were all decreased significantly， while the level of HDL-C was increased significantly （P＜0.05 or P＜0.01）. The plaque area in thoracic aorta and sinus lipid deposition in aortic sinus were decreased， and the ratio of aortic plaque area and the ratio of aortic sinus lipid lesion area were also decreased significantly （P＜0.05 or P＜0.01）. The macrophage infiltration of aortic sinus was decreased significantly， and its amount was also decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Compound dongchong xiacao oral liquid can inhibit the generation of AS plaque， the mechanism of which may be associated with the decrease of TC， TG and LDL-C levels in serum， the decrease of thoracic aorta plaque area， the reduce of aortic sinus lipid deposition and the macrophage infiltration.