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Previous studies have suggested that endothelins could be involved in the pathogenesis of target organ damage in diabetes. The aim of this study was to evaluate the possible protective effect of Bosentan, an antagonist of endothelin receptor, on the kidney of diabetic rats. The study comprised a control group of 10 WKY rats and a group of 22 WKY rats in which diabetes was induced by streptozotocin i.v.; 10 rats were the control group. Diabetic rats received insulin and mean blood glucose was approximately mS 400 mg/dl throughout the study; they were divided into two groups: 11 rats received Bosentan 100 mg/kg/die by gastric gavage and 11 received vehicle for 1 month. Twenty-four hour urine collection was performed before and at the end of the study. Urinary protein excretion rate was expressed as microg urinary protein/mg urinary creatinine. The renal collagen I, fibronectin, and TGFbeta were evaluated by means of immunochemistry. The statistical analysis of the results demonstrates that Bosentan has prevented the increase in urinary protein excretion and that of renal immunoreactive collagen I, fibronectin, and TGFbeta induced by diabetes without reducing blood pressure. This study suggests a new clinical application for the antagonists of endothelin receptors.