AbstractAims/hypothesis. To determine whether raxofelast, a new water soluble antioxidant decreases oxidative stress and improves endothelial function in men with Type II (non-insulin dependent) diabetes mellitus. Methods. We treated ten normotensive, normocholesterolaemic men with Type II diabetes and as controls ten healthy men matched with them for age with raxofelast (600 mg twice daily) for 1 week. Plasma 8-epi-PGF2, a non-enzymic oxidation product of arachidonic acid was measured by gas chromatography/mass spectrometry as an index of oxidative stress. Forearm vasodilator responses to brachial artery infusion of acetylcholine (7.5, 15 and 30 g min1) and of the nitric oxide donor nitroprusside (1, 3 and 10 g min1) were measured by strain gauge plethysmography. Results. Plasma concentrations of 8-epi-PGF2 were greater in diabetic than in control men (0.99 0.20 vs 0.18 0.01 nmol l1, means SEM, p 0.001) and fell after raxofelast (from 0.99 0.20 to 0.47 0.07 nmol l1, p 0.05) in diabetic men but not in control men. Blood flow responses to acetylcholine were lower (p 0.05) in diabetic than in control men (7.4 1.0 vs 12.9 2.3 ml min1 100 ml1 for the highest dose). In diabetic men, but not in control men, raxofelast increased (p 0.05) blood flow responses to acetylcholine (from 7.4 1.0 ml min1 100 ml1 to 11.3 2.3 ml min1 100 ml1 at highest dose). Blood flow responses to nitroprusside were similar in control and diabetic men and in both groups were similar before and after raxofelast. Conclusion/interpretation. Oral treatment with raxofelast for 1 week reduces oxidative stress and improves endothelial function in men with Type II diabetes. [Diabetologia (2000) 43: 974977]