Introduction: Adult stem cells can differentiate into various lineages including cardiomyocytes and endothelial cell via cardiomyoangiogenesis. This study evaluates the hypothesis that intravenous injections of bone marrow mononuclear cells (BMCs) could improve myocardial contractility and promote myocardial survival in doxorubicin (Dox) induced cardiomyopathy. Methods: Adult male Sprague-Dawley rats were induced to develop dilated cardiomyopathy by Dox. 5-FU-treated stem cell enriched BMCs (2.5x10E7) were injected into the vein after cessation of two-week treatment of Dox. The localizations of transplanted cells were evaluated one week after the injection of PKH67-labeled BMCs. Immunohistochemical and immunoblot studies were carried out two weeks after BMCs injection. Results: Cell-treated rats showed significant improvement of left ventricular percent fractional shortening compared to the control (83.5짹8.3% vs. 69.2짹6.5%, p<0.01). Histologic analysis demonstrated that cell-treated rats attenuated the increment of ventricular interstitial collagen deposition and had improved capillary endothelial cells compared with the control. PKH67-labeled BMCs distributed well in heart tissues. Cell proliferation by BrdU and Ki-67 immunostaining were noted in cell-treated heart. Cardiac CXCR4 protein expression showed a 80.3% increase at day 7 (p<0.01) and day 14 in the cell-treated group, but only at day 14 in the control group. The relative ratio of myocardial phosphorylated Akt/total Akt revealed a 16.8 % increase (p<0.05) in day 7 in cell-treated group compared with control group. Conclusion: These data indicate that stem cell enriched BMCs can function to improve myocardial contractility and promote myocardial survival in Dox induced cardiomyopathy.