Background: Doxorubicin (DOX) is highly effective anti-neoplastic agent, but it has side effects including cardiotoxicity. Moringa oleifera and vitamin E are potent antioxidants that prevent cardiotoxicity. Objective: evaluate the possible protective role of moringa oleifera and vitamin E on doxorubicin-induced cardiotoxicity. Materials and Methods: Sixty-five adult male albino rats were randomly divided into five groups. Group I (control group). Group II (affected group): rats were injected intraperitoneally with a cumulative dose of 15 mg/ kg of DOX for three weeks. Group III (moringa group): given in a dose of (500 mg/ kg/ day) by gastric tube orally for four weeks. Group IV (vitamin E group): given in a dose of (100 mg/ kg/ day) by gastric tube orally for four weeks. Group V (moringa and vitamin E). Heart specimens were taken and prepared for histological, immunohistochemical and EM examination. Results: Group II showed disorganized, widely separated muscle fibers, cytoplasmic vacuolation, pyknosis of many cardiomyocyte nuclei, the mitochondria appeared distorted, extravasation of RBCs and inflammatory infiltrations. There was significant increase (P