There is evidence that fructose-1,6-diphosphate (FDP) provides protection from hepatic and cardiac toxic-induced damage and ischemic renal insult. To determine if FDP also protects against cyclosporine (CsA)-induced nephrotoxicity, two groups of adult male Wistar rats were studied for whole kidney clearance rates. After two initial control periods, group 1 received only CsA (CsA, n = 8). Group 2 received FDP 350 mg/kg, followed by CsA 50 mg/kg (FDP-CsA, n = 6). In both groups, after a 30-min equilibration period, two additional clearance rates were measured (Postl and Post2). A significant reduction in clearance rates was observed after drug infusion in both groups (approximately 58 and 64% in CsA and FDP-CsA groups, respectively, p < 0.05) with a recovery to control values in the Post2 period in the FDP-CsA group. These data suggest a protective effect of FDP on CsA-induced renal impairment.