Aim To investigate pathogenesis of atherosclerosis,three methods for establishment of rat animal model were compared. Methods Three different methods,including high lipid only, high lipid+ Vitamin D overload, and high lipid+ Vitamin D overload+ endothelium injure, were used for inducing atherosclerosis in rats. After 90 days, serum lipid, serum calcium, morphology change of thoracic aorta were determined,and immunohistochemical assay of macrophage and (-smooth muscle actin were performed. Results The levels of serum total cholesterol (TC),triglyceride (TG),LDLC in three groups(hyperlipidemia group,hyperlipidemia + vitamin D3 group,and hyperlipidemia + vitamin D3 + endothelium denudate group)were obviously higher than those in control group (p<0.01). The levels of serum calcium in two groups(hyperlipidemia + vitamin D3 group and hyperlipidemia + vitamin D3 + endothelium denudate group)were also obviously higher than those in control group and hyperlipidemia group (p<0.01). Compared with control group,there were thicker intima,thinner media in hyperlipidemia + vitamin D3 group and hyperlipidemia + vitamin D3 + endothelium denudate group(p<0.05 and p<0.01). By immunohistochemistry,the CD68 positive level were low in hyperlipidemia group and hyperlipidemia + vitamin D3 group,and high in hyperlipidemia + vitamin D3 + endothelium denudate group. The α-actin positive level in intima is thick in hyperlipidemia + vitamin D3 group,thin in hyperlipidemia + vitamin D3 + endothelium denudate group.The rats treated with high lipid only showed hyperlipidemia without As lesion ;the rats treated with high lipid+ Vitamin D overload showed fibrous plaque; the typical mature atheromatous plaques were presented in the rats treated with high lipid+ Vitamin D overload+ endothelium injure creates mature atheromatous plaque. Conclusions Rat can be used as a ideal model for research atherosclerosis.The mature atheromatous plaque may created by high lipid + Vitamin D overload and endothelium injure.