Objective: To investigate the effect of monosodium glutamate (MSG) on the structure of the von Ebner’s salivary gland (VEGs).Design: 5 different groups were created, (control group I) in which rats fed on regular diet, (group II) received10g MSG/mixed with 100g basal diet daily, (group III) received 20g MSG with same route of administration;first 3 groups were sacrificed after 2 months, (group IV) received 10 g MSG, (group V) received 20g MSG; last 2 groups were sacrificed after4 months. Histological structures of examined tissues of different groups were studied. In addition, immunohistochemical localization of S-100 protein was conducted. Results: Inflammation and degenerative changes were observed in the tissues of (VEGs), especially in the salivary acini of different groups in comparison to control. The severity of such degeneration increased with higher doses for longer periods reaching peak in last group with complete degeneration of most of acinar cells. Similar to this, immunohistochemistry demonstrated increased expression of S100 within tissues serous acini and ducts of experimental groups compared with control. Conclusion: MSG presented a dose-time dependent degenerative and inflammatory effect on von Ebner’s salivary gland that endanger the salivary flow.