Cyclophosphamide, a cytotoxic alkylating agent, is an extensively used antineoplastic agent. Cardiotoxicity is considered as one of the limiting side effects of its use, which is attributed to oxidative stress. Zingiber officinale is powerful antioxidants against free radicals and oxidative attacks. The aim of this study is to investigate the possible protective effects of Z. officinale against cyclophosphamide induced cardio-toxicity in adult male albino rats. We used 30 adult male albino rats, divided into five groups; Group Ia (-ve control), Group Ib (+ve control), Group II (Z. officinale treated group; 200 mg/kg/day orally), Group III (cyclophosphamide treated group; single dose of 150 mg/kg I.P.), and Group IV (cyclophosphamide and Z. officinale treated group; rats received Z. officinale as before followed by single dose of cyclophosphamide (150 mg/kg)). At the end of experiment, we studied biochemical parameters: oxidative markers (MDA, GSH and Catalase), and Troponin i. The heart tissue was examined by light and electron microscope to evaluate histo-pathological changes and immunehistochemical technique for localization of inducible nitric oxide synthase (iNOS) in the cytoplasm of cardiomyocytes. The result showed increase in troponin I and disturbance of oxidative markers in cyclophosphamide treated group compared to control groups. Whereas these results had significantly improved in cyclophosphamide and Z. officinale treated group. Light and electron microscopic examination revealed disruption in the heart tissue histo-architecture in cyclophosphamide group with strong positive cytoplasmic iNOS immunoreaction in numerous cardiomyocytes by histochemical examination unlike that in cyclophosphamide and Z. officinale treated group which returned near normal. In conclusion, cyclophosphamide has a cardiotoxic effect which can be prevented by Z. officinale supplementation. Further studies about cyclophosphamide toxic effect on the heart and about Z. officinale role in protection are recommended.