Background: Monosodium glutamate (MSG), a sodium salt of glutamic acid is commonly used as flavor enhancer in Chinese, Japanese and ready to serve foods all over the World, is the inducer of oxidative stress. In the present era, MSG and alcohol is becoming a part of daily food. Concomitantly, there is a tremendous increase in the incidences of cardiovascular diseases. So, the present study was designed to elucidate the effect of MSG by evaluating the changes in oxidative stress markers in cardiac tissue of normal and alcoholic adult male mice. Materials and Methods: Animals were divided into six groups of six mice each and MSG at dose levels of 0, 4, and 8 mg/g body weight was given orally for seven consecutive days (that is from 31st day to 37 th day of alcohol ingestion) to chronic alcoholic (30% ethanol/100 g body weight) adult male mice. After the dose period (38 th day), animals were fasted overnight, sacrificed by decapitation and hearts were removed for the estimation of lipid peroxidation (LPO), xanthine oxidase (XOD), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) and its metabolizing enzymes like glutathione peroxidase (GPx) and glutathione reductase (GR). Results: A significant (P < 0.001) increase was observed in LPO and XOD levels while a significant decrease (P < 0.001) in the levels of SOD, CAT, GSH, GPx and GR was found in cardiac tissue of normal and alcoholic animals. Conclusion: These observations suggested that oral ingestion of MSG at dose levels of 4 mg/g body weight and above with and without alcohol increased the oxidative stress and thereby, could act as an additional factor for the initiation of atherosclerosis.