To evaluate the protective effect of diabetes mellitus (DM) on renal function of rats treated with gentamicin (GM), male Wistar-EPM rats (250-350 g) were treated with streptozotocin (SZ; 45 mg/kg) and starting 10 days after induction of diabetes, GM was given for ten consecutive days at a daily dose of 40 mg/kg. In the GM-treated group (G), a significant fall in inulin and sodium-p-amino-hippurate clearance was obtained (3.57 +/- 0.16 and 12.59 +/- 0.61 ml min-1 kg-1 vs 6.43 +/- 0.21 and 17.98 +/- 0.47 ml min-1 kg-1 in control rats (C), respectively) while in the animals previously injected with SZ (diabetic+gentamicin, DG group) these changes were not observed. The diabetic (D), G and DG groups showed a significant rise in urinary flow compared to C (0.165 +/- 0.009, 0.145 +/- 0.007 and 0.173 +/- 0.009 ml min-1 kg-1 vs 0.109 +/- 0.003 ml min-1 kg-1, respectively); however, only in G was the U/P inulin ratio significantly decreased when compared to C. The fractional excretion (FE) of sodium and potassium was significantly augmented in G when compared to C, D and DG. Thus, diabetes protected against gentamicin nephrotoxicity at both the glomerular and tubular level, although it did not promote a reduction in urinary flow.