Backgrounds: Antioxidative effect of HMG-CoA Reductase Inhibitor has recently been noted as one of their pleiotrophic effects.Advanced glycation endproducts(AGE) induced smooth muscle cell proliferation and formation of reactive oxygen species are emerging as one of the important mechanism of diabetic vasculopathy, but little is known about antioxidative action of statin on AGEs. We hypothesized that HMG-CoA Reductase Inhibitor may reduce the AGEs-induced increased intracellular oxidative stress in VSMCs. Methods: Rat aortic smooth muscle cell culture was done using the different levels of AGEs stimulation in the presence or absence of simvastatin. Cell proliferation was measured using MTT colorimetric assay. Western blotting was performed to assess the activation of MAPK system in the cultured VSMC. HMG-CoA Reductase Inhibitor was treated for inhibition experiment. AGE stimulated VSMC was incubated with 0, 1 and 10 關M of activated simvastatin for 1h before inhibition experiment, and followed by quantitative analysis of the cell proliferation with MTT assay. The formation of ROS were evaluated by H2DCFDA reagent.Carotid balloon injury was also performed in OLETF diabetic rats that were pretreated for 1 week with statin. Results: AGEs stimulation was associated with increased VSMC proliferation and was associated with increased ERKs, p38, COX-2, c-jun, NF캡B. Increased ROS formation by AGEs was noted. Compared with the control, statin inhibited AGE-stimulated VSMC proliferation by dose dependent manner. Statin also inhibited the activity of MAPKs induced by ROS formation with AGE treatment. Neointima formation after balloon injury was much thicker in AGE-stimulated OLEFT rats than in control, but no further neointimal growth was observed in OLEFT rats treated with statin after balloon injury. siRNA-mediated silencing of RAGE expression had no effect on the change of ERK, p38 and COX-2, c-jun and NF캡B mediated by statin. Conclusions: In vitro and in vivo data suggest that AGEs play a key role in VSMC proliferation and increase the oxidative stress. Statin inhibited the AGE-induced proliferation of VSMCs and suppress the ERKs activity increased by the ROS formation.