Pharmaceutical interventions targeting proteins that regulate VSMC growth and movement are promising new approach to treat diabetes-associated cardiovascular disease. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand-activated transcription factor in the nuclear receptor superfamily. Thiazolidineodione (TZT) insulin sensitizers are pharmacologic ligands for PPARgamma. All of the major cells in the vasculature express PPARgamma, including endothelial cells. VSMCs, and monocytes/macrophages. PPARgamma ligands may protect the vasculature against injury by inhibiting cell growth and movement, improving endothelial function, and suppressing tissue inflammation. Antiproliferative effects of PPARgamma ligands are mediated by targeting critical cell cycle regulators, including Rb and p27(Kip1), that regulate the progression of cells from G1 phase into S phase to conduct DNA synthesis. Pharmacologic activation of PPARgamma in vascular cells may provide a novel therapeutic approach to retard diabetes-associated vascular disease.