The ligand-activated transcription factor peroxisome proliferator activated receptor gamma (PPAR款) is a key factor in adipogenesis, insulin sensitivity, cell cycle regulation and differentiation. PPAR款 also exerts several vascular effects that may include anti-inflammatory and anti-atherogenic actions, as well as inhibitory effects on proliferation and migration of various types of cells such as vascular cells, monocytes and endothelial cells. We therefore investigated the effects of antidiabetic PPAR款 activator (troglitazone, TRO) on the HUVECs proliferation and the signaling pathways involved. TRO (1~20 關M) significantly inhibited serum-induced proliferation of HUVEC in concentration–dependent manner. However, 2 關M of a PPAR款 antagonist GW9662, pretreatment failed to reverse the anti-proliferative action of TRO, suggesting the effect was PPAR款 independent. Serum-stimulated Akt-activation in HUVECs was attenuated by 10 關M TRO pretreatment, and the phosphorylation of PTEN, a natural inhibitor of the PI3K/Akt, was also attenuated. We then tested the effect of TRO on the casein kinase 2 (CK2) activity, an upstream regulator of PTEN. TRO pretreatment in HUVECs suppressed serum-increased CK2 activity. And the inhibitor of CK2, DRB treatment was accompanied with anti-proliferation in HUVECs. In conclusion, our results suggest that TRO inhibits cellular proliferation of HUVECs through suppression of casein kinase II activity, and that this inhibitory action of TRO may be mediated by PPAR independent pathway.