Monosodium glutamate (MSG) is one of food enhancer that is commonly used worldwide, and fewer studies were done about its cardiovascular effects which is common cause of morbidity and mortality in human. This study was designed to assess the cardiotoxicity of MSG and to evaluate the potential modulatory antioxidant effect of quercetin which is a natural polyphenolic flavonoid. fifty adult albino rats were divided into five equal groups: negative control; positive control; quercetin treated; MSG-treated and “MSG + quercetin” treated. A single daily dose of quercetin (50mg/kg) and MSG (4g/kg) were given orally for 45 days according to the study regimen. The present study illustrated cardiotoxic effects of MSG evidenced by a significant increase in the serum creatine phosphokinase (CK-MB) activity, cardiac troponin I (cTnI) level and tissue malondialdehyde level (MDA) along with significant decrease in tissue glutathione-s- transferase (GST) level; and histological changes in cardiac architecture (cloudy swelling with fiber separation and vascular congestion. & hemorrhage) in MSG treated group. The addition of quercetin with MSG showed significant improvement of previously mentioned changes.