Abstract: Objiective: Cardiac muscle cells play a critical role in maintaining the normal function of the heart. Cardiotrophin-1(CT-1), a potent cardiac survival factor, is capable of inhibiting apoptosis or promoting survival in cardiomyocytes. We sought to elucidate the mechanism of CT-1 promoting cardiac myocyte survival in cultured neonatal rat cardiomyocytes. To explore the potential signaling pathway that might be responsible for this effect. Methods: We examined the cardiac myocyte survival effect of CT-1 in cultured neonatal rat cardiomyocytes. The cardiomyocytes were stained [3-（4，5-dimethyl－thiaziazol-2-yl）-2-5-diphenyltetrazolium bromide，MTT] and counted. Results: The survival rate of cardiac myocytes was increased by CT-1 in a dose-dependent manner (10-10～10-7 mol/L) and in a time-dependent manner(1~4d, 10-8 mol/L) in cultured neonatal rat cardiomyocytes. Pretreatment of PD098059 (5×10-5mol/L) ，a MAPK blocker, decreased significantly survival rate of cardiac myocytes by promoted CT-1. The phorbol 12-myristate 13-acetate (PMA) (1×10-5mol/L)，a PKC activator, increased significantly this effect of CT-1,but inhibited significantly by MAPK blocker PD098059. Conclusion: These results indicate that CT-1 is a potent factor of promoting cardiac myocyte survival, and increase significantly survival rate of cardiac myocytes in a dose-dependent and a time-dependent manner in cultured neonatal rat cardiomyocytes. The MAPK signaling pathway mediates CT-1 induced cardiac myocyte survival .PKC signaling molecule may be a upstream signaling transduction pathway which cascades of MAPK in CT-1 induced cardiac myocyte survival .