This study aimed to evaluate the protective effect of rebamipide (free radical scavenger) against the nephrotoxic effect induced by cisplatin in normal rats. Twenty-four male Wister albino rats were divided equally into four groups: control, rebamipide, cisplatin and cisplatin plus rebamipide-treated groups. Nephrotoxicity was induced with single intravenous (i.v.) cisplatin dose of 6 mg kg(-1)and measured through the estimation of kidney weight, serum albumin (Alb), serum creatinine (Cr), blood urea nitrogen (BUN), kidney glutathione (GSH) and malondialdehyde (MDA) production. In the cisplatin-treated group the kidney weight as a percent of the total body weight, serum Alb, serum Cr, BUN, GSH content and MDA amount were: 0.61+/-0.054%, 2.84+/-0.24 g dl(-1), 2.99+/-0.10 mg dl(-1), 147.08+/-7.46 mg dl(-1), 3.11+/-0.238 micromol g(-1)and 1449. 09+/-127.36 nmol g(-1), respectively. All the previous changes were significantly (P<0.01) different from the corresponding values in the control group. In addition, histopathological examination of the kidney tissue revealed degenerative cellular material and apoptotic tubular cells were seen in the renal tubules. Rebamipide treatment (140 mg kg(-1), i.p.) for 1 week ameliorated all the previous changes and the results recorded for the cisplatin plus rebamipide-treated group were: 0.45+/-0.035%, 4.17+/-0.091 g dl(-1), 1.37+/-0.209 mg dl(-1), 72.25+/-5.14 mg dl(-1), 5.063+/-0.269 micromol g(-1)and 560.23+/-21.98 nmol g(-1)for the previous tests, respectively. Furthermore, significant improvement in the kidney histopathology was observed. The results of this study clearly revealed that rebamipide protected the kidney against the nephrotoxic effect of cisplatin. These results suggest that lipid peroxidation is not the only mechanism by which cisplatin induced nephrotoxicity. More investigations are needed to confirm the effect of rebamipide and at the same time to elucidate the exact mechanism by which cisplatin induces nephrotoxicity.