Background and purposes: The precise molecular mechanism of adriamycin-induced cardiomyopathy(ADR-CM) is still unknown. This study was intended to analyze the mechanism of apoptosis induction and the effect of blocking Fas/Fas Ligand interaction with neutralizing anti-Fas Ligand antibody link with myocardiac performances in acute and chronic ADR-CM in rats. Methods : Cardiotoxicity was induced in rat by intraperitoneal administration of ADR weekly 2 mg/kg (chronic-IgG group, n=13 and chronic-anti FasL group, n=13) or every other day 5-6 mg/kg (acute-IgG group, n=6, and acute-anti FasL group, n=6) to total amount of 16 mg/kg with (acute and chronic-anti FasL groups) or without (acute and chronic-IgG groups) intravenous neutralizing anti-Fas Ligand antibody injection. Same amount of saline and normal mouse Ig G serum were injected to the control group. Initial and follow up echocardiographic evaluation was performed after completion of the drug administration. TUNEL assay and immunohistochemical stain for examination of Fas, Bax, and Bcl-2 protein overexpressions were performed. Fas protein overexpression was examined with western blotting. Results: The systolic thickness of IVS(interventricular septum), LVPW(left ventricular posterior wall) and EF(ejection fraction), FS(fractional shortening) were significantly decreased in chronic-IgG group compared with those parameters of control group or chronic-anti FasL group (p<0.05). Peak mitral E velocity(82.0짹11.1 vs 44.0짹11.0 cm/sec, p<0.05) and E/A(2.45짹0.3 vs 1.1짹0.6, p<0.05) in pulsed Doppler examinations were diminished in acute-IgG group compared with control group. The TUNEL positive nuclei were dominant in experimental groups compared with control group. In chronic-anti FasL group, the TUNEL positive nuclei were significantly fewer than in chronic IgG group (62.9짹14.6 vs 36.6짹11.2 %, p<0.05). Conclusion : Apoptosis plays an important role in both acute and chronic ADR-CM. The Fas/Fas Ligand interaction is important in the induction of apoptosis in ADR-CM independent of mitochondrial pathway and can be interrupted with neutralizing anti Fas Ligand antibody.