Acute kidney injury (AKI) is a rapid loss of renal function. It has high mortality rates. Still, renal replacement therapy is considered the best solution for recovering AKI. This opens a line of thought to develop an alternative therapy for it without complications. Mesenchymal stem cells are considered a new therapy for treating kidney diseases. The aim of this work was to address the anti-apoptotic, antioxidative, and pro-angiogenic effects of adipose tissue-derived MSCs (AD-MSCs) and bone marrow-MSCs (BM-MSCs) for treating AKI. Adult male Wistar rats were assigned into nine groups (n = 10): (1) the control group; (2) the AKI group, receiving cisplatin; (3) the AKI group treated with ADMSCs (1 × 106); (4) the AKI group treated with AD-MSCs (2 × 106); (5) the AKI group treated with AD-MSCs (4 × 106); (6) the AKI group treated with losartan; (7) the AKI group treated with BM-MSCs (1 × 106); (8) the AKI group treated with BM-MSCs (2 × 106); and (9) the AKI group treated with BM-MSCs (4 × 106). The results showed a significant rise in creatinine, urea, and cystatin C (cys C) levels and upregulation of p38 mRNA, whereas a significant decline in NAD(P)H quinone oxidoreductase 1 (NQO-1) protein and downregulation of B-cell lymphoma-2 (Bcl-2) mRNA and vascular endothelial growth factor (VEGF) mRNA were recorded in AKI. MSCs could improve renal functions manifested by decreased urea, creatinine, and cys C levels; downregulation of p38; and upregulation of Bcl-2 and VEGF. Moreover, MSC therapy could induce NQO-1 in the treated rats relative to the untreated rats. So, cell-based therapy can reduce AKI through the antioxidative, anti-apoptotic, and pro-angiogenic properties of MSCs. Therefore, the findings received in this attempt create a fertile base for the setup of cell therapy