Objectives: Monosodium Glutamate (MSG) is one of the world's most extensively used food additives which are ingested as part of commercially processed foods. MSG is a slow excitotoxin food additive which can cause generation of numerous amounts of free radicals which affects many organs such as heart. Vitamin C is an antioxidant protects the body against oxidative stress. Methodology: the experiment was carried out on 100 albino rats weighing about (150-200) g. The animals randomly were divided into equal 4 groups (n=25/group).The first group was served as control , the second group was administered oral doses of Vit.C (200 mg/Kg), the third group was administered oral doses of Monosodium Glutamate (MSG) dissolved in distilled water equal to 60 mg/kg daily (60 mg/Kg) the fourth group was administered oral doses of Monosodium Glutamate (MSG) dissolved in distilled water equal to 60 mg/kg daily (60 mg/Kg) and Vitamin C (200 mg/Kg) for 90 days respectively. Heart tissue oxidative stress biomarkers (Glutathione "GSH" and Mucosal Lipid Peroxidation "MDA") were estimated spectrophotometrically. Cardiac dysfunction biomarkers as protein kinase C (PKC) and troponin-I (Tn-I) were estimated using ELISA. Immunohistochemically, tissues caspase-3 and tumor necrosis factor- alpha (TNF-α) were estimated. Histopathology: Samples from heart were fixed in Formalin 10% for 48 h. Routine histological procedures followed by routine hematoxylin and eosin stain and Masson's trichrome stains for collagen identification. Results: In control negative and vitamin C group, a normal histological structure of cardiac muscles could be found. Vitamin C administration corrected the disturbances caused by MSG. Conclusions: MSG may produce oxidative stress via the generation of highly toxic oxygen and nitrogen free-radicals and the inhibition of several antioxidant enzymes, altering several physiological and functional changes in the heart; this resembles human myocardial infarction, which causes sudden death in humans. Vitamin C administration showed their cardiac protective effects.