Objective- Tissue factor (TF) is the primary molecule that initiates coagulation cascade and then triggers thrombus formation. Its expression is known to be induced by paclitaxel, which may be one of the underlying mechanisms for the increased risk of paclitaxel-eluting stent thrombosis. PPAR-gamma agonist, rosiglitazone, has various beneficial actions on vascular cells. Here, we investigated the effect of rosiglitazone on TF expression that was aggravated by paclitaxel. Methods and Results- Rosiglitazone inhibited TF expression in response to thrombin in a concentration-dependent manner in human umbilical vein endothelial cells (HUVECs), human acute monocytic leukemia cell line (THP-1) and human umbilical vein smooth muscle cells (SMCs). TF expression in response to thrombin in these cells was exaggerated by the addition of paclitaxel. This aggravation of TF expression by paclitaxel was reversed by rosiglitazone in all cell types. The inhibitory effect of rosiglitazone on TF expression was mediated by decreased phosphorylation of the mitogen-activated protein (MAP) kinases. The underlying mechanisms varied depending on cell type; HUVECs appeared to be dependent on c-Jun terminal NH2 kinase (JNK) and p38; THP-1, dependent on p38 and p42/44 (ERK); SMCs, dependent on JNK and ERK. In contrast to TF, rosiglitazone did not suppress expression of TF pathway inhibitor. In rat carotid artery balloon injury model with paclitaxel continuous infusion through intravascular pump, co-administration of rosiglitazone reduced TF expression in the injured vasculature. Conclusions- In vitro and in vivo, rosiglitazone reversed the paclitaxel-induced aggravation of TF expression in vascular cells via MAP kinases inhibition. These data suggest that rosiglitazone would be a potential therapeutic option for prevention of stent thrombosis in patients with paclitaxel-eluting stents.