Monosodium Glutamate (MSG) is worldwide food additive commonly used as a flavor enhancer. Although its consumption can be regarded as harmless, yet histopathological changes in the gastric mucosa were described with prolonged consumption of MSG. The objective of the present study was to evaluate effects of MSG on the gastric mucosa. Thirty adult male albino rats (n=30) were used in this study. The animals were randomly divided into two equal groups (n=15 rats): Group A (Control); each rat daily received 2ml distilled water and Group B (Treated); each rat daily received MSG at a dose of 2mg/kg body weight dissolved in 2 ml distilled water. One set of sections were stained with H&E, Mallory trichrome stain and Periodic Acid Schiff (PAS) stain and another set were immuno-histochemically-stained to detect the proliferating cell nuclear antigen (PCNA). The gastric mucosa of MSG-treated rats revealed atrophic changes with ulcer formation and shedding of surface epithelium into the gastric lumen bases. The area of mucous neck cells showed many cells with a strong brown positive PCNA expression. Quantitatively, as compared to control group, the gastric mucosa revealed reduced thickness, widening of gastric glands and gastric pits and increased PCNA positive cells in MSG-treated group. Therefore, very low doses of MSG could produce histopathological changes in the gastric mucosa of rats and its safety as food additive in humans must be reconsidered.