[Background] Cisplatin is a widely used chemotherapeutic agent used to treat solid tumors, such as ovarian cancer, testicular cancer, head and neck cancer, and non-small cell lung cancer. However, one of its side effects is renal failure. In this study, we established a cisplatin-induced renal failure model in rats and investigated the inhibitory effect of orally administered magnesium oxide against it. [Methods] Renal function was evaluated in terms of plasma creatinine (Cre) and blood urea nitrogen (BUN), and the plasma magnesium concentration and body weight were used as indicators of general condition. Cisplatin 7.0 mg/kg was administered intraperitoneally on day 0. Magnesium oxide was administered orally at 200 or 400 mg/kg/day from day -3 to day 1 or from day -3 to day 0. [Results] During the period from day -3 to day 0, the increases in the plasma levels of Cre and BUN level induced by cisplatin were suppressed more significantly by magnesium oxide at 400 mg/kg/day than at 200 mg/kg/day. Magnesium oxide at 400 mg/kg/day had a greater preventive effect on cisplatin-induced nephropathy than at 200 mg/kg/day. Also, the preventive effect of magnesium oxide was higher from day -3 to day 1 than from day -3 to day 0. Examination of parameters overall suggested that body weight improved more rapidly in rats that received magnesium oxide than in rats that did not. [Conclusion] This study revealed that oral administration of magnesium oxide at a dose of 400 mg/kg/day from 3 days before to 1 day after administration of cisplatin had a marked preventive effect against cisplatin-induced renal failure in this rat model.