Circulating bone marrow derived immature cells, including CD34-positive (CD34(+)) cells, contribute to maintenance of the vasculature, not only as a pool of endothelial progenitor cells (EPCs), but also as a source of growth/angiogenesis factor. We hypothesized that the thiazolidineone compound pioglitazone could stimulate the circulating CD34(+) cells in diabetic patients. Thirty-four patients with type 2 diabetes received 15-30 mg pioglitazone for 24 weeks. The number of circulating CD34(+) cells significantly increased at 12 and continued this effect for 24 weeks (1.08+/-0.39, 1.34+/-0.34 and 1.32+/-0.28cells/microl at 0, 12 and 24 weeks, respectively). The change of CD34(+) cell levels (DeltaCD34(+) cells) between 0 and 12 weeks was significantly correlated with the change of high sensitive C reactive protein levels (Deltahs-CRP) and change in adiponectin levels (Deltaadiponectin) (r=-0.412, r=0.359, respectively). Our study demonstrated that pioglitazone treatment increased circulating CD34(+) cells, suggesting that this effect may at least partly contribute to the anti-atherosclerotic action of pioglitazone.