Doxorubicin (Adriamycin) is a potent chemotherapeutic agent for the treatment of a variety of human malignancies. Among several different mechanisms proposed for explaining the pathogenesis, increasing oxidative stress appears to play a major model that has been shown to increase free radical producing and decrease activities of endogenous antioxidant enzymes. There is an early depression in glutathione enzymes such as reduced glutathione, glutathione peroxidase and glutathione-s-transferase. Cardiomyopathy is also associated with apoptosis which precede the development of cardiotoxicity and congestive heart failure. Many different approaches have been used to minimize the incidence of doxorubicin-induced cardiomyopathy. In the present study, the rabbit model, the development of cardiomyopathy was prevented by reducing oxidative stress using natural antioxidant vitamin E (50 IU/kg body weight) and flavonoids morin, rutin and quercetin, which are generally available in the natural diet. The four weeks treatment of flavonoids (20mg/kg body weight) were affectively ameliorated the oxidative stress induced cardiomyopathy in rabbits by doxorubicin (10mg/kg body weight) treatment for two days. The flavonoids alter the biochemical parameters at optimum levels. The oxidative markers (lipid peroxidation, catalase, reduced glutathione, and glutathione-s-transferase) were significantly maintained by the flavonoids in blood. The overall conclusion of this study is that the flavonoids can act as antioxidants in the body and they can protect the biochemical and oxidative markers at optimum levels. By this study, the author suggests that rabbits are good experimental models to conduct various types of experiment in Biochemistry and Pharmacology and the diet rich flavonoids can useful in the protection of certain diseases like cardiomyopathy (CAD, hypertension, heart failure and stroke), diabetes, cancers and oxidative stress etc.,