Background: The chemotherapeutic drug methotrexate (MTX) is administered for managing multiple kinds of cancer. Aim: To determine if bone marrow mesenchymal stem cells (BM-MSCs) might protect rats against renal damage brought on by MTX. Materials and Methods: Rats were divided into five groups : (i) Control group received 2.5 ml saline. (ii) group received MTX as a single IP of 20 mg/Kg body weight. (iii) LEUK group: Benzene-induced leukemia group was injected intravenously every 2 days for 3 consecutive weeks by 0.2 ml benzene. (iv) LEUK/MTX group was injected intravenously every 2 days for 3 consecutive weeks by 0.2 ml benzene and treated by intraperitoneal injection of 2.5 mg/kg.bw/week MTX for 4 consecutive weeks. (v) (LEUK/ MTX/MSCs) group was injected intravenously every 2 days for 3 consecutive weeks by 0.2 ml benzene and treated by intraperitoneal injection of 2.5 mg/kg.bw/week MTX for 4 consecutive weeks. This group was also left for 8 days for kidney injury induction then injected intravenously with a single dose of 3x106 MSCs. After 4 weeks of MSCs transplantation. Kidney histopathology, Catalase and Superoxide dismutase activities as well as Capase-3 expression levels were examined. Results: Methotrexate induced marked pathological lesion which characterized by focal necrosis, cell infiltration and high immuno-expression of TGF-β1. Besides, treatment with MSCs successfully improved the severe effects of MTX on the kidney and restored histological architecture which confirmed by oxidative enzymes and apoptosis marker detection. Conclusion: MSCs have the capacity to protect against kidney fibrosis and might be employed as adjuvant treatment.