The effect of alpha-lipoic acid (LA) on the cardiotoxicity induced by doxorubicin (DOX) was investigated. A single dose of DOX (15 mg kg(-1), i.p) induced cardiotoxicity manifested biochemically by a significant elevation of serum creatine phosphokinase (CK; EC: 2.7.3.2) and lactate dehydrogenase (LDH; EC: 1.1.1.27) 48 h later. Moreover, cardiotoxicity was further confirmed by the significant increase in lipid peroxides measured as malondialdehyde (MDA), and significant decrease in protein thiols (Protein-SH) content in heart tissues. Administration of LA (100 mg kg(-1)) orally for 5 days before and 2 days after DOX injection produced a significant protection against cardiotoxicity induced by DOX. The amelioration of cardiotoxicity was evident by significant reductions in serum CK and LDH. Moreover, LA prevented the rise of MDA as well as the significant reduction of Protein-SH. These results may suggest that LA has a protective effect against cardiotoxicity induced by DOX and it may, therefore, improve the therapeutic index of DOX.