Aim Cardiotrophin-1(CT-1) is a member of interleukin-6(IL-6) family of cytokines.CT-1 plays a role in inducing cardiomyocyte hypertrophy and promoting cardiomyocyte viability.We sought to elucidate effect of CT-1 inducing atrial natriuretic peptide (ANP) mRNA expression and its underlying mechanism in cultured neonatal rat cardiomyocyte. Methods The cardiomyocytes of neonatal rat were isolated and cultured with method of pre-plating for different time.The ANP gene of cardiomyocytes was measured with reverse transcription polymerase chain reaction(RT-PCR) approach. Results The ANP/GAPDH ratio of cardiac myocytes were increased by CT-1 in a dose-dependent manner(10-9,10-8 and 10-7 mol/L) in cultured neonatal rat cardiomyocytes.The ratio were respectively 1.18±0.14,1.58±0.20 and 2.03±0.30.And the ANP/GAPDH ratio were also augmented by CT-1 in a time-dependent manner(1,3,5 d,10-8 mol/L),respectively 1.16±0.18,1.47±0.17 and 1.97±0.24.Pretreatment of PD098059(50 μmol/L),a extracellular signal regulated kinase 1/2(ERK1/2) blocker,increased significantly ANP mRNA expression of cardiac myocytes induced by CT-1(ANP/GAPDH ratio 1.94±0.15),whereas Calphostin C,a protein kinase C(PKC) blocker,10 μmol/L,effected no significantly on this role induced by CT-1. Conclusion These results indicate that ANP mRNA expression induced by CT-1 increased significantly in a dose-dependent and a time-dependent manner in cultured neonatal rat cardiomyocytes.The MAPK(ERK1/2) signal pathway mediate the effect of CT-1.The PKC signaling molecule may no take part in directly the effect of CT-1.