Aim: Doxorubicin, a widely used antineoplastic agent in clinical practice, has a serious side effect, cardiotoxicity. Due to the risk of life-threatening cardiotoxicity which limits the therapeutic potential, diagnosis and prevention of doxorubicin-induced cardiotoxicity becomes critical. Free radicals, lipid peroxidation and antioxidant enzymes are suggested to be involved mainly in doxorubicin-induced cardiotoxicity pathogenesis. The aim of this study was to evaluate the pathogenesis of doxorubicine induced cardiotoxicity and the effect of L-tryptophan on it. Material and Methods: The study was designed on three groups: the first group received (n=10 young rabbit) 6 daily doses of intraperitoneal doxorubicine (cumulative dose 15mg/kg) for 15 days. The second group received (n=10 young rabbit) received triptofan (200 mg/kg/day oral) 24 hours before intraperitoneal doxorubicine and this was continued 7 days after the last dose of doxorubicine. The third group was the control group (n=7). Myocardial and plasma glutathione peroxidase (GSH-Px). superoxide dismutase (SOD), and malondialdehyde (MDA) activitiy and myocardial nitric oxide (NO) activity was measured in our rabbit model. Serum troponin I (Tn I) and creatine kinase MB (CKMB) values were tested for diagnostic value of cardiotoxicity. Results: Our results suggested that doxorubicin formed severe cardiotoxicity in young rabbits with 15 mg/kg cumulative doses with markedly decreased myocardial GSH-Px and increased MDA and NO values. L-tryptophan reduced doxorubicin-induced cardiotoxicity by increasing myocardial GSH-Px and SOD activity. Although serum Tn I and CKMB levels had diagnostic values, any change in plasma GSH-Px, SOD and MDA activity was determined in assessing doxorubicin-induced cardiotoxicity. Conclusion: In conclusion, decreased antioxidant enzyme levels, increased free radicals and lipid peroxidation play a major role in the pathogenesis of doxorubicin-induced cardiotoxicity and tryptophan is an effective antioxidant in reducing doxorubicin-induced cardiotoxicity.