Introduction: Recent evidence suggests an antiproliferative effect of thiazolidinediones in the vascular wall. Thiazolidinediones are known to inhibit vascular smooth muscle cell proliferation by reducing mitogen induced degradation of p27Kip1 resulting in increased activity of Retinoblastoma protein(RB). However, the upstream signaling mechanisms associated with the above mentioned mechanism has not been elucidated. The mTOR is a key regulatory kinase that plays a major role in the mammalian cell cycle, and the Rapamycin eluting stents have proven to significantly reduce the rate of coronary stent restenosis in human clinical trials. In this study, we hypothesize that Rosiglitazone, a PPAR-款 agonist, inhibits vascular smooth muscle cell proliferation through the inhibition of PDK-Akt-TOR-p70S6 kinase signaling pathway. Method: Rat aortic VSMCs were prepared from thoracic aorta of 200-250g male Sprague-Dawley rats. The cells were divided into group 1(high glucose exposure 450mg/dL, insulin 1關M/L) and group 2(low glucose exposure 100mg/dL insulin 1關M/L). The cells were treated with PPAR-g ligand rosiglitazone (~10 關M/L) before the addition of 1 關M/L insulin. Cell proliferation was measured using the thiazolyl blue tetrazolium bromide (MTT) colorimetric assay (Sigma). Western blot analysis and RT PCR was performed to determine whether inhibition of the Akt and mTOR signaling pathway by Rosiglitazone is associated with subsequent antiproliferative response. Results: Vascular smooth muscle cell proliferation was significantly suppressed by rosiglitazone in a dose-dependent manner. Western blot analysis demonstrated significant inhibition of phosphorylation of Akt, m-TOR, and p70S6K regardless of the expression levels of Akt, m-TOR, and p70S6K in cells treated with rosiglitazone. The up-stream regulator of p70S6K, PI3K was inhibited and the down-stream signal transducer of p70S6K was suppressed by rosiglitazone. Conclusion: The inhibitory effect of rosiglitazone on vascular smooth muscle cell proliferation stimulated with insulin is mediated by the inhibition of Akt-m-TOR-p70S6K pathway. Further studies to demonstrate the inhibition of this pathway in vivo is needed. 關關關關關關關關關關關關關