Objective: to study the possible cardioprotective effect of ACE inhibitors; captopril and fosinopril versus that of vitamin F on doxorubicin-induced cardiotoxicity. Material & methods', female albino rats were used and divided into 5 groups each included 36 rats. One group used as a control (group I) and other four groups were given 15 injections of doxorubicin IP with a total cumulative dose of 15 mg/kg. In group II doxorubicin was given alone. While, group III was given doxorubicin +captopril (20 mg/kg/day), group IV was given doxorubicin + fosinopril (10 mg/kg/day) and group V was given doxorubicin + vitamin E (45 mg/kg/day). At the end of the 3rd, 9th and 15th weeks, the animals in the different groups were examined for changes in; body weight, mean arterial blood pressure, ECG, cardiac contractility and cardiac histopathology. Results: Dox administration resulted in significant cardiac toxicity while simultaneous administration of ACE inhibitors or vitamin E with DOX could significantly improved the doxorubicin-induced cardiotoxicity. Conclusion: it could be concluded that; initiation of ACE inhibitors with doxorubicin treatment can be considered a potential strategy to "protect" against the development of the delayed sequelae of doxorubicin on the heart and this effect was more or less comparable to that of vitamin E in rats.