The study showed the effect of MSCs and antioxidants on amelioration of acute kidney injury induced by ischemia-reperfusion and the different possible underlying renoprotective mechanisms. It was carried on 60 male Sprague-Dawley rats (body weight 170-220 g). Rats were divided into 6 groups as follow: Group 1 (Sham group), where 10 rats were subjected to right nephrectomy without exposure to left renal pedicle ischemia, (Group 2) Positive control group, where 10 rats were subjected to right nephrectomy and left renal ischemia, (Group 3) Treated 1 group, where 10 rats were subjected to right nephrectomy and left renal ischemia. This group was received DPPD (0.5 g / kg, i.p.) 24 hours before the induction of ARF, (Group 4) Treated 2 group, where 10 rats were subjected to right nephrectomy and left renal ischemia. This group was received DPPD (0.5 g / kg, i.p.) 24 hours after the induction of ARF, (Group 5) Treated 3 group, where 10 rats were subjected to right nephrectomy and left renal ischemia. This group was received DPPD (0.5 g / kg, i.p.) 48 hours after the induction of ARF, (Group 6) Treated 4 group, where 10 rats were subjected to right nephrectomy and left renal ischemia. This group was received MSCs, which were processed and cultured for 14 days, in a dose of (106) by IV infusion at the rat tail vein 24 hours after the induction of ARF. After 4 days of induction of the acute renal failure rats were sacrificed to obtain renal tissue, blood, urine specimens. As aresult, I/R group showed marked thrombosis in glomerular capillaries with disrupted glomerular basement membrane, Leukocytic infiltration (glomerular necrosis), marked tubular necrosis, interstitial haemorhage and inflammation and normal blood vessels. Serum levels of B-NAcetylglucosaminidase (NAG), urea and creatinine were significantly elevated. Lipid peroxidation showed marked elevation. Both MSCs and antioxidant ameliorated I/R-induced nephrotoxicity to a great extent and showed significant anti-renal injury.