Background Nitric oxide (NO), which is a potent vasodilator substance and is thought to have antiatherosclerotic properties. On the other hand, NO activity reduces in metabolic syndrome and metabolic syndrome is associated with induction of a proinflammatory and oxidative stress, and endothelial dysfunction. Endothelial dysfunction is an important early sign of atherosclerosis in metabolic syndrome. The aim of this study was to investigate the effect of pioglitazone on endothelial function in terms of plasma NOx and circulating inflammatory markers. Methods We randomized 28 subjects with the metabolic syndrome assigned to receive 15mg of pioglitazone per day (PIO, n=16) during 3 months or placebo group (PLA, n=12). To estimate the endothelial function, Flow-mediated dilatation (FMD) and nitroglycerin-induced, endothelium-independent vasodilatation (NMD) were measured in brachial artery by using vascular ultrasound. Plasma NOx and inflammatory markers, as ESR, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 were measured before and at the 12-week follow-up. Plasm NOx was measured by Griess method. Results After 12 weeks of therapy, FMD, reflecting the endothelial function and responsiveness to blood flow, improved in PIO (from 6.7짹6% to 11.7짹5%: P< 0.01), but not in PLA, whereas NMD, reflecting the vasodilatation by smooth muscle, was not changed significantly in both group. The level of plasma NOx was increased in PIO (from 64.8짹18mol/L to 92.7짹23mol/L: P< 0.01), but not in PLA. Plasma levels of hsCRP and IL-6 were dropped significantly (from 2.6짹2.1 mg/dl to 0.91짹0.9 mg/dl and 20.9짹1.3 pg/mL to 14.6짹0.4 pg/mL: P<0.05) in PIO, not in PLA. Conclusions Administration of PPAR-款 agonist in metabolic syndrome patients improves endothelial function enhancing the production of NOx and reducing proinflammatory markers. PPAR-款 agonist may be able to modulate the progression of atherosclerosis.