Background: Doxorubicin is an effective chemotherapeutic drug that commonly induce pathological alteration in skeletal muscles. Bone- marrow mesenchymal stem cells (BMMSCs) offer a therapeutic potential for tissue repair and regeneration. Tumour necrosis factor-alpha (TNF-α) and Interleukin-1 beta (IL-1β) display worthy biomarkers for tissue damage and repair. Objectives: The aim of the current study was to evaluate the therapeutic effect of BMMSCs on doxorubicin - induced skeletal myopathy in experimental animals, through histological studies, antioxidant activity and investigation of TNF-α, IL-1β as diagnostic parameters for muscle damage and regeneration. Methodology: 40 adult albino-rats were divided into 4 equal groups; Group-I (control group) injected with phosphate-buffered saline (PBS), Group-II: doxorubicin- induced myopathy model group; received no treatment, Group-III: doxorubicin- induced myopathy model left for spontaneous muscle recovery, and Group-IV: doxorubicin- induced myopathy treated with systemic BMMSCs. The skeletal muscle regeneration evaluated through histological and antioxidant activity studies and investigation of TNF-α, IL-1β and vascular endothelial growth factor (VEGF) levels. Results: Photomicrographic studies of the muscle fibers showed a more evident regeneration in MSCs treated groups (IV) when compared with the other groups received no treatment. A significant reduced levels of TNF-α, IL-1β, and increased both VEGF and antioxidant activity were demonstrated in group IV when compared with the other groups received no treatment. Conclusion: MSCs is a promising therapy for doxorubicin-induced skeletal myopathy. TNF-α, and IL-1β are helpful biomarkers for evaluation of SCs therapeutic efficacy.