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Doxorubicin is an effective anti-neoplastic agent application of which has been limited due to its cardiotoxic side effects. Lithium is widely used for treatment of neuropsychiatric symptoms in bipolar disorders. Lines of evidence point to the cardioprotective effects of lithium against heart injuries. The current study aims to investigate the protective effects of lithium against doxorubicin-induced cardiotoxicity in rat model. Male Wistar rats were treated with 300 mg/kg p.o. lithium in their water supply and/or doxorubicin (1.25 mg/kg, i.p.), four times per week for four weeks. General conditions, mortality rate and body weight were measured during the experiment. At the end of the experiment, ECG parameters and papillary muscle contractility force were assessed. Serum samples were collected to measure the lithium concentrations as well as cardiac troponin T level (cTNT, a biomarker of cardiac injury). In addition, heart weight was measured and the cardiac tissues were evaluated both macroscopically and microscopically. The results of the present study indicate that lithium might diminish mortality rate, general toxicity (edema, alopecia and cachexia), improve S(alpha)-T segment and QT interval prolongations as well as heart contractility force. Application of lithium could inhibit the increase of cardiac troponin T and formation of myocardial lesions. These outcomes show the protective effects of lithium against doxorubicin-induced cardiotoxicity in rat. On the whole, the results of the present study suggest that lithium might be considered as a new indication for the prevention of doxorubicin-induced cardiotoxicity., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)