Investigation was carried out to study protective effect of some renin inhibitors in acute nephrotoxicity on forty male Sprague Dawely rats weighting 200g to 250g which divided into four equal groups each group included 10 rats GroupI (Control group): was fed on normal ration for one month. While GroupII (cisplatin group) was injected i.p. by 7.5 mg kg B.W of cisplatin for one month. GroupIII (captopril group) was injected i.p. by 60 mg kgB.W of captopril for one month.GroupIV (captopril plus cisplatin group) there is injection of cisplatin (7.5mg/kg b .wt) i.p and within one hour it is proceeded by i.p injection of captopril (60 mg/kg b. wt) daily for one month. At the end of experiment the obtained results revealed that, administration of cisplatin and captopril caused a highly significant decrease in serum and kidney MDA ,serum creatinine concentration , serum blood urea nitrogen concentration, serum angiotensin II concentration and serum aldosterone level. whole blood and kidney p53 concentration compared to cisplatin treated rats .Also there was highly significant increase in whole blood GSH concentration, serum Glutathione peroxidase, serum catalase activity, serum superoxide dismutase activity and serum renin concentration compared to cisplatin treated group. Administration of cisplatin only revealed in increase in serum and kidney MDA ,serum creatinine concentration , serum blood urea nitrogen concentration, serum angiotensin II concentration serum aldosterone level, whole blood and kidney p53 concentration as compared to control group . There was a highly significant decrease in whole blood GSH concentration, serum Glutathione peroxidase, serum catalase activity, serum superoxide dismutase activity and serum renin concentration compared with control group. Administration of captopril only result in decrease in serum and kidney MDA ,serum creatinine concentration , serum blood urea nitrogen concentration, serum angiotensin II concentration serum aldosterone concentration, whole blood and kidney p53 concentration compared to control group also there was highly significant increase in whole blood GSH concentration, serum Glutathione peroxidase, serum catalase activity, serum superoxide dismutase activity and serum renin concentration when compared to control group. These results were supported by histopathological examination which revealed some alterations represented by that the tubule was dilated and shrinked or atrophied , the tubular cells was removed and lost and there is asignificant destruction of glomerular with penetration of leuococyte and intratubular bleeding. While administration of cisplatin and captopril result in regenerating glomeruli and tubules of kidney tissues produce by cisplatin administration.