Background and Aim: The use of Doxorubicin (Dox) to treat various tumors is limited by its cardiotoxicity. This study aimed to compare the cardioprotective potential of vitamin E versus liposomal-Dox against cardiotoxic effects on the structure of left ventricle. Materials and Methods: Fifty male albino Wistar rats (180-220g) were divided into control (I), Dox (II), vitamin E with Dox (III) and liposomal-Dox (IV) groups. Groups II, III and IV received Dox and liposomal-Dox (3mg/kg) at days 1, 3, 5, 7, 9 and 11. Group III received Vitamin E (100mg/kg) daily with Dox administration. At day 12, blood was collected and left ventricles were dissected and prepared for LM and EM study. Results: Serum lactate dehydrogenase, creatine phosphokinase and creatine kinase-MB increased by 2.5 folds in Dox-treated rats compared to control rats, but decreased in vitamin E and liposomal-Dox groups compared to Dox group. The maximal decrease was in liposomal-Dox group with values near to control. LM examination of left ventricle from Dox-group showed hemorrhagic areas between widely separated cardiomyocytes containing pyknotic nuclei. Inflammatory cells and adipocytes were seen in the interstitium. EM of Dox group showed variable sized mitochondria with ruptured cristae inbetween fragmented myofibrils. LM and EM examination of ventricles from vitamin E and liposomal-Dox groups showed mild changes with liposomal-Dox group appeared near to control. Left ventricular fiber diameter was decreased in Dox group compared to control group with nearly normal diameter in liposomal-Dox group. Area percent of collagen fibers increased and the optical density of desmin immune-expression was reduced in Dox group compared to control and liposomal-Dox groups which were alike. Conclusion: Dox-induced structural changes of rat ventricle were diminished by concomitant vitamin E intake. Liposomal-Dox administration-only- was more effective in reducing these changes; hence, it can accomplish a successful clinical target to decrease Dox-associated cardiotoxicity.