Propolis is one of the major hive products of bees and is rich in flavonoids, which are known for antioxidant activities. It is well known that the chemical properties of phenolic acids or flavonoids, in terms of the availability of the phenolic hydrogens as hydrogen donating radical scavengers, predict their antioxidant properties. In this study, the flavonoids scavenging activity of propolis has been exploited to obtain protection against the peroxidative damage in rat heart mitochondria which was induced by the administration of an acute dose of doxorubicin (20 mg kg(-1), i.p). The peroxidative lesions were evaluated biochemically and biophysically, 24 H after DXR administration. Abnormal biochemical changes in heart mitochondria from DXR treated rats including a marked increase in both malondialdehyde (MDA) and anion superoxide production; decrease both of respiratory chain ratio (RCR= V3/V4) and P/O. Pretreatment of rats with propolis extract, given per os (100 mg/kg/day) during four days prior to DXR injection, substantially reduced the peroxidative damage in the heart mitochondria: we showed significant reducing both of mitochondrial MDA formation and production of superoxide anion, restoration of RCR and P/O and reducing of rate and the amplitude of mitochondrial swelling. The data demonstrate that antioxidants from natural sources may be useful in the protection of cardiotoxicity in patients who receive doxorubicin and as reported for its claimed beneficial effect on human health by biomedical literature.