Consumption of diets rich in fats or sugars is correlated with the onset of insulin resistance and hypertension in rats. In the present study, rats were fed diets that induce hypertension; 50% of the rats were also treated with pioglitazone, a thiazolidinedione derivative that sensitizes target tissues to insulin and decreases plasma insulin concentration in insulin-resistant animals. Pioglitazone treatment prevented the development of hypertension and reduced plasma insulin concentration by 70% and 37% in rats fed a high-fat or glucose diet, respectively (P < .05 compared with rats fed the same diet without pioglitazone). In rats fed a control diet, neither insulin nor blood pressure (BP) was affected by pioglitazone treatment. The effect of pioglitazone on insulin and BP could not be attributed to a reduction in body weight, since pioglitazone increased the weight gain of rats fed the high-fat or glucose diet. These findings suggest that in rats fed a diet high in fat or glucose, treatment with pioglitazone maintains plasma insulin concentration and BP at control levels, regardless of body weight.