The PPAR family of nuclear hormone receptors consisted of three subtypes (慣, 棺/灌, and 款) is ubiquitously expressed in various tissues and known to be involved in lipid and glucose metabolism. Unlike PPAR慣 and PPAR款, the effect of PPAR灌 on VSMC proliferation has not been elucidated in details yet. Here we investigated the effect of L-165041, a selective PPAR灌 ligand, on rVSMCs proliferation and neointima formation. In vitro study showed that L-165041 inhibited rVSMC proliferation in a dose dependent manner by blocking the G1 to S phase progression as evidenced by increased G0/G1 but decreased S phase. Furthermore, repressed phosphorylation of Rb by L-165041 also contributed to its anti-proliferative effect. L-165041 also inhibited PDGF-induced expressions of both cyclinD1 and CDK4, and PDGF-induced rVSMCs migration was suppressed by L-165041 in a dose dependent manner. For in vivo study, rat carotid artery balloon injury model was employed. The rats received L-165041 (100關g/kg/day) for 14 days using osmotic mini-pump showed an approximately 25% reduction of neointima formation compared to control group. In summary, our results suggest that PPAR灌 ligand inhibits rVSMC proliferation, and the underlying mechanisms include repression of Rb phosphorylation and key molecules in cell cycle progression. Although the administration of L-165041 only showed marginal reduction of neointima formation in the present study, there still is a possibility that L-165041 can be used an agent to control neointima formation at a higher dose. Our study will help us better understand the role of PPAR灌 in cardiovascular system.