Background: Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. Weinvestigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-inducednephrotoxicity in rats. Materials and Methods: In this study, 40 female Wistar rats were randomly dividedinto five equal groups. The first group, which served as the control, was administered physiological saline (2.5cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose)plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose ofVE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The ratswere sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase(GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes weremeasured. Results: The histopathological injury score, plasma levels of MDA, urea, creatinine were found toincrease in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased(p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se-VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatininelevels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused byCDDP were also significantly improved after Se-VE treatment (p<0.05). Conclusions: Oxidative stress increaseswith CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention ofCDDP-induced nephrotoxicity in patients.