Objective To investigate the regulating effects of PI3-K/Akt signaling pathway BR>on the differentiation of the marrowderived cardiac stem cells (MCSCs) induced with BMP2 toward cardiomyocytes and to determine the possible mechanisms in signal transduction on differentiation of MCSCs toward cardiomyocytes. Methods MCSCs were selected from the bone marrow of SD rats with singlecell cloning culture. The differentiation of MCSCs toward cardiomyocytes was induced with 10 μg/L BMP-2, and changes in p-Akt levels in MCSCs were examined with Western blotting and immunocytochemistry using several time points after induced with the BMP-2. Effect of PI3-K was detected with the PI3-K inhibitor Ly294002 Expression of Nkx2-5、GATA-4 and cTnT、Cx-43 mRNA of MCSCs before and after induction were determined with RT-PCR . After induction with BMP-2, the morphological alterations to the cells were examined under a phase contrast microscope. Results MCSCs express ckit and the early cardiac transcription factors Nkx2-5. Before induction with BMP-2,the p-Akt level in MCSCs was low. After induction with BMP-2, the p-Akt level in MCSCs was increased and was to reach a peak at 20 to 30 min and subsequently decreased at 1 hour. After treatment with the PI3-K inhibitor Ly294002, p-Akt level of the cells was decreased significantly. RT-PCR detection showed that expression of Nkx2-5 and GATA-4 were weak before induction; however expression of Nkx2-5 and GATA-4 was increased at two weeks and conspicuous at four weeks after induction. Expression of cTnT and Cx-43 mRNA was not observed before induction, and was obvious at two weeks and even stronger at four weeks after induction. After treatment with Ly294002, the expression of Nkx2-5, GATA-4, cTnT and Cx-43 mRNA was reduced significantly, although no morphological change to the cells was obvious. Conclusion BMP-2 may induces differentiation of MCSCs toward cardiomyocytes, and the PI3-K/Akt signali