Backgrounds: Antioxidative effect of HMG-CoA Reductase Inhibitors(statin) has recently been noted as one of their pleiotrophic effects. Advanced glycation endproducts (AGEs) induced smooth muscle cell proliferation and formation of reactive oxygen species(ROS) 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 statin may reduce the AGEs-induced increased intracellular oxidative stress in VSMCs and analyze the possible mechanism of action of statins in the ROS-induced cellular signaling. Methods: Rat aortic smooth muscle cell(RASMC) culture was done using the different levels of AGEs (human glycated albumin, Sigma aldrich Chemical) stimulation in the presence or absence of simvastatin. Cell proliferation was measured using the MTT assay (Sigma). Western blotting was performed to assess the activation of MAPK system in the cultured VSMC. AGE stimulated RASMC was incubated with 0, 1 and 10 關M/L of activated simvastatin for 1h before inhibition experiment, and followed by quantitative analysis of the cell proliferation with MTT assay. The activity of ERKs, phosphorylated ERKs, NF캡B and the formation of ROS were evaluated by immunoblotting technique and H2DCFDA reagent, respectively. Results: Increasing concentration of AGEs stimulation was associated with increased VSMC proliferation and was associated with increased phosphorylation of ERK, NF캡B , JUN, and p-38. Increased ROS formation by AGEs was noted. Compared with the control cells (without simvastatin treatment), simvastatin inhibited AGE-stimulated VSMC proliferation by dose dependent manner. Simvastatin inhibited the ERKs activity induced by ROS formation with AGE treatment dose dependently. Conclusions: In vitro data suggest that AGEs play a key role in VSMC proliferation and increase the oxidative stress. Simvastatin inhibited the AGE-induced proliferation of VSMCs and suppress the ERKs activity increased by the ROS formation. Activation of MAPK system and increased ROS formation may be the possible mechanism of AGEs induced vasculopathy and statin may play a role in AGEs induced diabetic atherosclerosis.