Objective To compare the effects of forming atherosclerosis by conducting ballon injury operation after 1th, 2th and 3th week of Vitamin D₃(VD₃) i.p., exploring the best method for atherosclerosis modeling. Methods 36 male rats were selected for balloon-injured carotid artery. SD rats were divided into 4 groups randomly: control group (n=6), Model group1 (n=10), Model group2(n=10), Model group3 (n=10). Control group were fed up with common diet. Model groups were fed up with high-fat diet and injected 4.0×10⁵IU/kg VD₃ through enterocoelia in the beginning, followed by the balloon-injured left carotid artery operation after 1th, 2th and 3th week respectively and 1.0×10⁵IU/kg VD₃ injection at 0th, 2th week after operation. The rats were killed at 4th week after operation. The serum levels of TG, TC, HDL-C and LDL-C were checked. ELISA was used to detect the content of hsCRP, IL-6 and TNFα. HE staining was used to observe the pathological changes in the thoracic aorta, and the thoracic aorta thickness, plaque area(PA), cross-sectional area of vessel(CVA) and the ratio of PA to CVA(PA/CVA) were analyzed. Results After 4 weeks of operation, levels of TC and LDL-C were significantly increased in Model group2 and 3 compared with that of the control group (P<0.05). Furthermore, contents of hsCRP, IL-6 and TNFα of model groups were also seriously higher than that of the control group (P<0.05), and that of Model group 3 were the highest. Typical AS plagues were observed in different degrees in model groups, and thoracic aorta thickness and PA/CVA were obviously increased than that of control group (P<0.05). Model group 3 turned out masses of lipid foam cells accumulated, and PA, CVA and PA/CVA were significantly increased than that of Model group2 or 3. Conclusion The AS model can be established successfully in rats with ballon injury after 3 weeks of high-fat diet plus VD₃ i.p., which is the ideal method to induced atherosclerosis model.