The prevalence of obesity is rapidly rising to epidemic proportions around the world at an alarming rate. Obesity is associated with numerous complications including significantly increased risks of diabetes and cardiovascular diseases. Epidemiological studies report an inverse association between dietary flavonoid consumption and mortality from cardiovascular diseases. The aim of this work was to study the vascular effects of dietary supplementation of red wine polyphenols extract, Provinols™, in the Zucker fatty rats (ZF). Rats received normal diet or supplemented with Provinols™ (20 mg/kg/day) for 8 weeks. Vascular reactivity was assessed and tissular content of NO and superoxide anion (O2-) production were measured. Provinols™ reduced the change in body weight. Systolic blood pressure was not different among the groups and was neither affected by Provinols™. In the aorta, Provinols™ improved endothelium-dependent relaxation to acetylcholine (Ach) without affecting that of the NO donor, sodium nitroprusside. Provinols™ did not modify contraction induced by phenylephrine (Phe). The NO synthase inhibitor, L-NAME, increased to the same extent contraction to Phe in vessels from the two groups. The non-selective cyclooxygenase (COX) inhibitor, indomethacin, and the COX-2 selective inhibitor, NS398, reduced the response to Phe in aorta from both groups. However, the contraction to Phe was greater in Provinols™ in presence of indomethacin. In small mesenteric arteries, Provinols™ did not affect both the relaxation to Ach and the contraction to Phe. Provinol™ increased vascular (aorta, carotid and small mesenteric arteries) NO release that was accompanied with a decrease of O2- production. The later occurred via reduction of NF-κB and Nox-1 stainings in the aorta. In summary, Provinols™ increase NO production, reduce both oxidative stress and inflammatory process both in conductance and resistance arteries from ZF rats. This effect is associated with improved endothelial function and reduction of the participation of vasoconstrictor metabolites from COX within the aorta. Altogether, these results point out beneficial effects of plant-derived polyphenols on endothelial function and vascular reactivity in obese rats.