This study tested whether implanted embryonic stem cell-derived early-differentiated cells (EDCs) lead to improvement in cardiac function by preventing cardiac apoptosis in aging rats after myocardial infarction. Cardiac apoptosis after transplantation of EDCs was assessed in situ by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling reaction (TUNEL) staining as well as by measurements of protein levels of cleaved caspases 3, Bax, and Bcl-2. Our results indicate that cell transplantation improved cardiac function at 6-months observation. The frequency of apoptotic cells in the peri-infarcted myocardium 3 days after cell transplantation was significantly decreased in the cell transplantation group. EDC therapy decreased the protein levels of cleaved caspase 3 and Bax, and increased the level of Bcl-2 in comparison to myocardial infarction control. Additionally, the number of apoptotic cells decreased significantly in cardiomyocytes precocultured with EDCs. This study demonstrates that functional improvement of EDC transplantation may at least in part be related to a reduction in cardiomyocyte apoptosis.