Introduction: Recent report has shown that advanced glycation end products(AGEs) are reported to have a role in neointimal formation in animal experiment of arterial stenosis. AGE mediated cross link formation of proteins such will not only result in stiffening of the arteries, but result in increased extracellular matrix formation and increased vascular inflammation resulting in higher risk of neointimal proliferation. In this study, we investigate whether Algebrium chloride, an AGE cross link breaker, will have a role in inhibiting neointimal proliferation in diabetic rat carotid artery balloon injury model. Method: Sprague-Dawley (SD) rats weighing 200 to 250grams received Streptozocin at 80mg/kg intraperitoneally. Sixteen weeks later, the rats were randomized into two study groups: 5 diabetic rats receiving placebo and 5 diabetic rats receiving Alagebrium 10mg/kg was treated for 4 weeks. After 4 weeks, the carotid artery balloon injury was performed. For the in vitro analysis, rat aortic VSMCs were treated with Alagebrium 1-10 關M added 24 hours before the addition of AGE as mitogenic stimulus. DCF fluorescence assay was performed to assess the formation of intracellular reactive oxygen species and Western blot analysis was performed to assess the expression of pMAPK. For the in vivo experiment, histologic sections were cut from the right carotid arteries and stained for morphometric analysis. Results: The in vitro study revealed a dose dependent effect of Alagebrium on AGE stimulated proliferation of RASMC. There was a significant dose dependent inhibition of AGE mediated reactive oxygen species formation by Alagebrium. This was associated with a dose dependent inhibition of pMAPK formation as well. This cellular mechanism was involved in the regulatory effect of alagebrium on AGE-induced CTGF and ECM expression in RASMC. The in vivo study revealed a significant inhibition of neointima hyperplasia in ballooned injured rats treated with Alagebrium compared to placebo. Conclusion: Alagebrium inhibited neointima formation in vivo and vascular smooth muscle cell proliferation in vitro. One of the mechanisms may be the inhibition of AGE mediated ROS formation with subsequent stimulation of MAPK pathway.