Purpose: To investigate the effect of adipose-derived mesenchymal stem cells (ADMSCs) on doxorubicin (DOX)-induced cardiomyopathy in rats. Methods: A total of 30 male Sprague-Dawley rats were randomized into control (n = 10) and study groups (n = 20). Control group received no intervention while the study group received DOX administered intraperitoneally (i.p.) six times daily at a dose of 2.5 mg/kg/ day. The study group was divided into 2 groups. One group received DOX + normal saline (0.9 %w/v) sodium chloride (NaCl) solution ntraperitoneally at a dose of 1 mL/kg/day. Another group received DOX + ADMSC at a dose of 2.0 x 106 cells/kg intraperitoneally twice a week. Biochemical parameters and histopathological changes in blood and heart tissue samples were compared among groups. Results: Caspase-3 immuno-expression, plasma malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), growth differentiation factor-15 (GDF-15), pro-brain natriuretic peptide (Pro-BNP), troponin, heart transforming growth factor–β (TGF-β) were significantly lower in DOX+ ADMSC compared to DOX + saline group (p < 0.05). However, caspase-3 immune expression and the number of regularly arranged cardiomyocytes significantly decreased in DOX + ADMSC group compared to DOX + saline group (p < 0.05). Conclusion: Adipose-derived mesenchymal stem cells (ADMSCs) reduce caspase-3 immunoexpression, restore cardiac histology, and ameliorate DOX- induced cardiac injury. Further investigation and clinical trials are recommended, especially to determine the continued safety and efficacy of AD-MSC-based therapy in cardiac injury.