Mesenchymal stem cells (MSCs) have generated a great deal of excitement and promise as a potential source of all types of cells for cell-based therapeutic strategies. The present study aimed to evaluate the ameliorative effect of MSCs injected via tail vein and sub-capsular in rats with ischemia reperfusion induced acute kidney injury. A total number of 72 Sprague dawely rats were used in this study and were divided into 3 groups: group (I): Negative control (n=18), group (II): ischemic reperfusion untreated ;(n=18) and group (III): ischemic reperfusion treated with MSCs (36 rats). group (III) was divided into two sub-groups : the first subgroup was treated with MSCs injected via tail vein;(n=18) and the second one was treated with MSCs injected subcapsular;(n=18) . six rats from each group and sub groups were euthanized at day1, days3, and day7 from beginning of the experimental study.for histopathological examination and Biochemical analysis was performed for serum creatinine, blood urea nitrogen (BUN), urine creatinine, kidney malondialdehyde (MDA), nitric oxide (NO).additionally to kidney injury lesion scores for kidneys tissue were performed in all experimental groups.Results of this study revealed that MSCs which injected sub-capsular in rats with ischemic reperfused acute renal injury induced ameliorative effects at day 7 through significant decreasing of serum creatinine, BUN, renal MDA, NO, renal fibrosis score and significantly increases creatinine clearance compared to rat sub-group treated with MSCs injected via tail vein.It was concluded that subcapsular injected MSCs in rats with ischemic reperfused ARI induced ameliorative effectcompared to tail vein injected MSCs in rats.