In this study, four kinds of atherosclerotic models with SD rats and ApoE-/- mice were established to select the best animal model for atherosclerosis.Methods Sixty male SD rats were randomly divided into three groups:the first group was fed on normal diets as control group; the second group was fed on high cholesterol diets as model 1 group; the third group was injected with a single dose of vitamin D3 and fed on high fat diet,which was model 2 group. Sixty C57BL/6 male mice including 20 wild type mice and 40 ApoE-/- mice which was divided into normal diet fed group as model 3 and high fat diet group as model 4. After 6 months, plasma lipids and inflammatory factors were detected, and the aorta was separated for oil red O and hematoxylin-eosin (HE) staining. Results Compared with the normal group, plasma total cholesterol (TC), interleukin 6 (IL-6) and C reactive protein (CRP) levels were significantly elevated(P＜0.05). But there's no difference between the three groups in plasma triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) levels(P＞0.05), and both of the two models didn't have atherosclerotic plaques and the characteristics of the early stages of atherosclerosis. In addition, compared with the normal group, plasma TC, TG, LDL-C, IL-6 and CRP levels of model 3 and model 4 were significantly elevated(P＜0.05), and were significantly higher in model 4 than model 3(P＜0.05). But plasma HDL-C levels of model 4 were significantly reduced(P＜0.05). Oil red O and HE staining showed that model 3 only had lipid deposition and small atherosclerotic plaques in aortic arch; but the model 4 had developed typical characteristics of atherosclerosis.Conclusion Both the two models of SD rats established with high cholesterol diets and high cholesterol diets + vitamin D₃ were not suitable for atherosclerosis research；Model 3 only had the early stage atherosclerotic characteristics；Model 4 mice had developed typical characteristics of atherosclerosis and were more suitable for atherosclerosis research.