Background: Doxorubicin (DOX) is a commonly used anticancer drug despite its dose-dependent cardiotoxic effects. The possibility of using stem cells to repair DOX-induced cardiotoxicity may open new therapeutic options. Aim of the work: To evaluate the role of mesenchymal stem cells (MSC) in recovery of both the structure and function of DOX-induced cardiotoxicity. Material and Methods: The study used ninety adult female albino rats divided into three equal groups; one control treated with saline, DOX group treated with doxorubicin 2.5 mg/kg every other day for two weeks, and DOX-MSC group treated with the same DOX regimen then injected one week after last DOX dose with DAPI-labeled male umbilical cord blood MSCs (UCB-MSCs). All three groups were evaluated at the 3rd and 6th weeks of the study by physical status, cardiovascular assessment in vivo, serum biochemical tests [malondialdehyde (MDA), total anti-oxidant capacity (TAC) and cardiac troponin I (cTnI)]. Results: DOX caused deterioration in general rat health, significant prolongation of QT interval and serum TAC, also caused an increase in serum MDA and cTnI. These findings aggravated at the 6th week in DOX group. Significant improvement of previous parameters in DOX-MSC group compared to DOX was detected at the 6th week. Homing of injected MSCs in rat hearts was confirmed by RT- PCR for male-specific Sry gene. Conclusion and Recommendations: UCB-MSCs have reparative effects on the damaged heart by ameliorating oxidative stress and relatively improving the function of the failing heart. This approach is worthy of serious consideration for clinical use.