Background: The pathogenesis of restenosis involves early inflammatory responses associated with the production of proinflammatory cytokines and growth factors, and subsequent fibrotic reactions related to vascular smooth muscle cell (VSMC) migration and proliferation. However, a precise mechanism for this biological function has not yet been clearly known. Recent evidence indicates that curcumin (diferuloyl methane), a major component derived from turmeric, Curcuma longa L., has low intrinsic toxicity and possesses a wide range of pharmacological activities, including anti-inflammatory, anti-thrombosis, anti-proliferative, and anti-oxidant activities. Therefore, curcumin may exert multiple suppressive effects on VSMC proliferation, thus reducing neointimal hyperplasia. To prove this hypothesis, cucumin were treated to rat aortic smooth muscle cell (RAoSMCs) and its anti- proliferative mechanism has been investigated. Methods: We treated curcumin to RAoSMCs and investigated its anti-proliferative mechanism. Cytoskeleton change that curcumin treated RAoSMC was characterized by 慣-tubulin staining, cell signaling was investigated by western blotting and RT-PCR, and apoptosis was demonstrated by annexin V binding, caspase-3 activity assay and DNA laddering. Also, proteome changes in RAoSMC were analyzed by two dimensional electrophoresis and MALDI-TOF mass spectrometry. Result: Curcumin inhibited serum and PDGF-stimulated proliferation of RAoSMCs in a dose-dependent manner by arresting G0/G1 phase of cell cycle, inducing apoptosis, and activation of PPAR gamma. The mRNA level of c-myc in PDGF-stimulated RAoSMCs was significantly reduced, and cytoskeleton was not changed in spite of cell shrinkage. In proteomics studies, we found that proteins which is participated in metabolism were reduced but heat shock protein or stress protein were increased. Conclusion: In this study, the molecular mechanism of the antiproliferative and apoptotic effects of curcumin in vascular smooth muscle cells have been investigated to determine which of transduction signals and genes are involved. These results suggest that the use of curcumin to inhibit atherosclerosis and restenosis.