Background: The cardiotoxicity of adriamycin (ADR) limits its clinical use as a anticancer drug. Although the precise mechanism by which it causes cardiac damage is not yet known, it has been suggested that apoptosis is the principal process in adriamycin-induced cardiomyopathy, which involves DNA fragmentation, cytochrome C release, and caspase activation. Cardiotrophin-1 (CT-1), a member of interleukin-6 superfamily, induces hypertrophy and prolongs survival of cardiac myocytes in vitro by inhibiting apotosis. The aim of this study was to investigate the cyto-protective effects of CT-1 against ADR-induced apoptosis in cardiac myocytes cell line, H9C2.Methods and Results: In cell survival test by CCK kit, ADR induced cell death in a dose dependent manner (50% death at 24 hours after 1 mM of ADR), and ADR cleaved caspase-3,. In RT-PCR, expression of Bax-a mRNA level increased, however, Bcl-2 decreased gradually through 24 hour of ADR treatment. The ratio of Bax-a/Bcl-2 mRNA peaked at 24 hours after ADR treatment. In contrast, CT-1 effectively attenuated the ADR-induced cell death in a dose-dependent manner. The changes of Bax-a and Bcl-2 mRNA expression after ADR treatment were reversed by CT-1 (I ng/ml) treatment. Furthermore, Akt phosphorylation increased by CT-1, which demonstrated that CT-1 inhibit by apoptosis induced by ADR. These data demonstrated that ADR-induced apoptosis of cardiomyocytes could be prevented by CT-1, therefore, it may possible to use CT-1 as a cardioprotective agent during ADR chemotherapy in patients with cancer.