Background and objectives: Acute renal injury (ARI) is a serious clinical problem without established regimen for treatment. Mesenchymal stem cells (MSCs) are undifferentiated cells that can differentiate and give rise to other cell types. The aim of the present work is to study the possible therapeutic role of MSCs in the treatment of the deleterious changes occurred in renal cortex and medulla of adult male albino rat model of ischemia/reperfusion (I/R) ARI.Material and methods: Forty adult male albino rats were used in this study. Animals were divided into four groups, 10 animals for each group. Group I is control sham-operated group. Three experimental groups were all subjected to I/R injury by clamping both renal pedicles for 40 min. These animals were further divided into three subgroups. Group II is non-MSC treated group. Group III (MSC treated group (local injection)): I/R animals received bromodeoxyuridine labeled BM-MSCs locally in renal cortex immediately after removal of the clamps and confirmation of reflow. Group IV (MSC treated group (systemic injection)): I/R animals that received single intravenous injection of bromdeoxyouridine labeled BM-MSCs in tail vein immediately after removal of the clamps and confirmation of reflow. Animals were sacrificed after 3 days of intervention. Serological measurements included serum urea and creatinine. Kidney specimens were processed for H&E, PCNA and Caspase-3. Real time RT-PCR study was done for TNF α and IL-6 gene expression.Results: Cortical and medullary renal tissue exhibited marked improvement histologically and serologically after MSCs treatment. The improvement was more obvious in case of systemic treatment. Conclusion:The present study shows the ability of MSCs to repair the structural and functional renal damage after I/R, Systemic route is more beneficial than local route. This may pave the future for therapeutic use of MSCs in the treatment of acute renal injury.