The aim of the present study was to investigate whether a dietary supplementation of alpha-lipoic acid could prevent blood pressure elevation, insulin resistance, and the increase in aorta superoxide anion production in a new experimental model of hypertension associated with insulin resistance. Sprague-Dawley rats were given 10% D-glucose in their drinking water combined either with a normal chow diet or with an alpha-lipoic acid-supplemented diet and were compared with control rats during 3 weeks. Oxidative stress was evaluated by measuring the aortic superoxide anion production using the lucigenin chemiluminescence method. Increases in blood pressure, insulin resistance, and aorta superoxide production observed in glucose-fed rats were prevented by the supplementation of the diet with lipoic acid. Positive correlations were found between aortic superoxide production and blood pressure, between insulin resistance and blood pressure, or between superoxide production and insulin resistance. Moreover, a decrease in the activity of plasma glutathione peroxidase observed in the glucose-fed rats was prevented by lipoic acid treatment. These findings demonstrate that high-glucose feeding rapidly induced hypertension and insulin resistance in association with the induction of a vascular oxidative stress. The antihypertensive action and the prevention of insulin resistance by lipoic acid appears to be associated to its antioxidative properties because it prevented the increase in oxidative stress, as reflected by the normalization of superoxide anion production in aorta and the prevention of the fall in the activity of glutathione peroxidase in the glucose-fed rats.