Introduction: Acute kidney injury (AKI) is a syndrome of rapidly declining renal function. Cisplatin nephrotoxicity is a major cause of AKI in about one third of patients under cisplatin treatment. Stem cell therapy have been suggested as a protective measure against cisplatin-induced AKI. The conditioned medium of the stem cells (serum-free culture medium) has been also found to minimize renal injury and might develop a new therapeutic strategy that avoids stem cells administration. Aim of the Study:This study was conducted to compare the effect of intravenous injection of bone marrow-derived mesenchymal stem cells (BMSCs) versus their conditioned medium (CM) in minimizing the cisplatin-induced acute renal injury. Material and Methods: Sixty adult female albino rats were divided into 4 main groups. Group (I) served as a control group, Group (II) (cisplatin treated group) that were subdivided into two subgroups IIa and IIb, Group (III) (BMSCstreated group) and Group (IV) (CM-treated group). Five young male rats were additionally used for obtaining the BMSCs. Rats of all groups were sacrificed on 4th day of the experiment, except for the rats of subgroup (IIa (which were sacrificed after one day of cisplatin administration. Renal specimens were prepared for histological and immunohistochemical techniques. Morphometrical studies and statistical analysis were performed. Results: Treatment by BMSCs resulted in obvious improvement of renal structure with significant increase in Proliferating Cell Nuclear Antigen (PCNA). However, conditioned medium (CM) was less effective in treatment of acute AKI. Conclusion: BMSCs administration is preferable than their CM in reversing the acute structural damage of the kidney induced by cisplatin.