Backgrounds: Advanced glycation endproducts (AGEs), irreversible non-enzymatic glycation of macromolecules enhance the local oxidant stress and immunoinflammatory reaction in diabetic vasculopathy through its receptor RAGE. Recently, AGEs have been reported to play a role in neointimal formation in the animal model of arterial injury. However, the potential role of AGE in vascular smooth muscle cell (VSMC) proliferation remains unclear. Therefore, we sought to determine whether the activation of VSMC proliferation by AGE is associated with activation of the mitogen-associated protein kinase (MAPK) system, an important signaling pathway associated with VSMC proliferation. Furthermore, we also investigated the association between serum level of AGEs with formation of ROS and expression of RAGE. Methods & Results: Blood samples were collected from the diabetic CAD patients and the serum levels of AGEs were analyzed by the fluorescent intensity method. In vitro smooth muscle cell culture was done using the different levels of AGEs containing serum of the patients. Smooth muscle cell proliferation was assessed using MTT analysis. Western blotting was performed to assess the activation of MAPK system and protein kinase C in the smooth muscle cells. Increasing concentration of AGEs was associated with increased smooth muscle cell proliferation and was associated with activation of ERK and Protein kinase C. The expression of RAGE was assessed by RT-PCR and the formation of ROS was evaluated using H2DCFDA. The possible inhibition of smooth muscle cell proliferation by AGE inhibitor, Aminoguanidine, was assessed. The formation of ROS was significantly correlated with increasing concentration of AGEs. Aminoguanidine (5-50 關g/ml) significantly inhibited activation of ERK and PKC by AGEs and inhibited the formation of ROS. Conclusions: High serum level of AGEs can indeed activates VSMC proliferation and increase the oxidative stress in vitro. Activation of ERK, PKC and increased formation of ROS may be the possible mechanism of AGEs induced vasculopathy. Aminoguanidines significantly inhibited smooth muscle proliferation through inhibition of AGEs and its receptor RAGE.