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Objective To investigate the serum expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) and C1q/tumor necrosis factor-related protein 3 (CTRP3) in type II diabetic rats with atherosclerosis and to undermine the interventional mechanism of simvastatin. Methods SD rats were randomly divided into normal diet (NC) group (n=8), high-fat diet (HFD) group (n=8), high-fat diet intervention (HFD+S) group (n=8), model (M) group (n=18) and model intervention (M+S) group (n=16). The diabetic atherosclerosis model was established by streptozotocin (STZ)+ Vitamin D3 (VitD3)+High-fat diet. The group HFD+S and group M+S rats were administrated with simvastatin at 20 mg/(kg⋅d)intragastrically as intervention while distilled water [20 mL/(kg⋅d)] were given to other groups. Serum levels of fasting plasma glucose (FPG), blood lipid, fasting insulin (FINS), VEGF, TGF-β1 and CTRP3 were compared between each groups. Results Characteristics of atheromatous plaque were seen in group M and group M + S whose pathological change were markedly attenuated compared to group M. Serum levels of VEGF, TGF-β1 and CTRP3 were significantly higher in rats from Group HFD than those in rats from group NC. Serum levels of VEGF and TGF-β1 were significantly higher in rats from Group M than those in rats from group NC. Serum level of VEGF was significantly higher in rats from Group M than it in rats from group HFD. Serum level of CTRP3 was significantly lower in rats from Group M than it in rats from group HFD. Moreover, serum levels of TGF-β1 and CTRP3 were significantly higher in rats from Group HFD+S than those in rats from group HFD after the intervention with simvastatin. Serum level of VEGF was significantly lower in rats from Group M+S than it in rats from group M, and serum levels of TGF-β1 and CTRP3 were significantly higher in rats from group M+S than those in rats from group M after the intervention with simvastatin. Conclusion VEGF, TGF-β1 and CTRP3 may participate in development of diabetic atherosclerosis. In addition to its hypolipidemic role, Simvastatin can also down regulate serum level of VEGF and up regulate serum levels of TGF-β1 and CTRP3 to exert a significant protective effect on diabetic atherosclerosis. [ABSTRACT FROM AUTHOR]