Objective: This is a study designed to explore the effects of different delivery modes of bone marrow-derived mesenchymal stem cells (MSCs) on cardiac function after myocardial infarction (MI). Methods: The expanded and purified MSCs were transplanted into the mice undergent the left coronary artery ligation throught the different delivery routes (intravenous delivery, or intramyocardial injection). Cardiac function was measured by echocardiography 2 weeks post delivery and the animals were sacrificed to pathologic detection. Results: These results showed cell delivery by the IM route could ameliorate the cardiac function and infarct size post MI, rather than by IV infusion.Conclusion: the optimal transplantation route likely plays an important role in cardiac cell therapy and the IM route may provide an advantage over IV infusion for cardiac function protection.