Introduction: Monosodium glutamate (MSG) is now used in many foodstuffs as a food additive and flavour enhancer. Although it has classified as safe food ingredient, the use of MSG remains controversial. MSG is a slow excitotoxin food additive which can cause generation of numerous amounts of free radicals which affects many organs such as liver. Vitamin C is an antioxidant and inhibits chemical carcinogenesis by protecting the body against oxidative stress. Aim of the study: Study role of antioxidant (vitamin C) on modulation biochemical, histological, histochemical and ultrastructural changes of liver caused by chronic use of MSG. Materials and Methods: Sixty adult albino rats divided into equal three groups, first group (control) received 1ml of saline daily for three months, Second group received MSG 6mg/g/BW/day for three months, third group received MSG 6mg/g/BW/day and vitamin C 500 mg /kg /b.w /day, orally and for three months. Biochemical changes were investigated by the liver function tests.  Assessment of histopathological changes of liver was done by using light microscope, transmission electron microscope, histochemical studies and immuohistochemical studies. Results: After chronic use of MSG, light microscope and transmission electron microscope examination revealed severe histopathological changes such as hepatic architecture destruction and dilatations of the central veins with statistical significant increase of liver enzymes. Histochemical studies revealed severe reduction of carbohydrates and proteins; pyknotic nucleus, vacuolated cytoplasm, swollen mitochondria and vesiculated rough endoplasmic reticulum with significant positive stained nuclei with ki-67 and p53. Administration of Vitamin C with MSG led to significant improvement of biochemical and pathological changes of liver. Conclusions: Chronic use of MSG caused hepatotoxicty of rats which is improved by administration of Vitamin C with it