Although monosodium glutamate (MSG) is commonly employed in the food industry, its possible toxic effects remain a concern. Vitamin E (Vit E), a strong lipid-soluble antioxidant, offers potential protection against oxidative damage caused by MSG exposure. To evaluate the protective effect of vitamin E against MSG-induced structural and molecular alterations in the dorsal surface of the tongue in albino rats. Thirty adult male albino rats were randomly assigned into three groups (n=10): Group 1 (Control) received saline for 40 days; Group 2 (MSG) received MSG (60 mg/kg/day) for 30 days; Group 3 (Vit E+MSG) received vitamin E (200 mg/kg/day) for 10 days prior to, and during, MSG administration. Tongue specimens were examined histologically, immunohistochemically for inducible nitric oxide synthase (iNOS), and by qRT-PCR for heme oxygenase-1 (HO-1) expression. Results: In MSG treated group, there was marked degeneration of filiform, fungiform, and circumvallate papillae with inflammatory infilteration. There was significant increase in iNOS immune reactivity (p<0.0001), and significant decline in HO-1 gene expression (p<0.0001) compared to control group. Vitamin E coadministrated group showed marked improvement in the histological damage, reducing iNOS immune reactivity by ~35% vs. MSG alone (p<0.05), and increasing HO-1 gene expression by ~2.4-fold compared to the MSG group (p<0.05). Conclusion: Vitamin E reinforcing its ameliorative effect against toxicity induced by MSG on the dorsal surface of the tongue in albino rats.