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Background: The consumption of fast-food is increasing among children, adolescents and adults. Carbonated drinks are widely consumed with fast food that also exists in the form of diet drinks as Diet Coke. One of the thousands of chemicals used in our new high-tech foods is the monosodium glutamate (MSG). Aim of the Study: This study was conducted to investigate the effect of Diet Coke and monosodium glutamate salt either separately or in combination on the cerebellar cortex and kidney of adult male albino rats. Materials and Methods: Twenty five adult male albino rats were divided into four groups. Group I: control group (10 rats) divided equally into two subgroups, subgroup IA in which rats had free access to food and water and subgroup 1B in which each rat administrated 0.5 ml of distilled water once daily by oral gavage. Rats had free access to food and water. Group II (5 rats): in which rats received Diet Coke instead of water throughout the day. Group DI (5 rats): in which each rat received 0.5m1 of MSG salt solution by dose of 3ern MSG/kgm by oral gavage once daily. Group IV (5 rats): in which each rat received Diet Coke instead of water throughout the day and 0.5m1 of MSG salt solution by dose of 3gm MSG/kgm by oral gavage once daily. Cerebella and kidneys were dissected out and processed for histological, immunohistochemical and morphometric studies. Results: Histological examination of the cerebellum and the kidney revealed that both Diet Coke and MSG either separately or in combination resulted in degenerative changes that were more significant in the combination group. The cerebellum showed degeneration of Purkinje cells and vaculations in the molecular layer. The kidney showed shrunken glomeruli, vacuolations of cells lining renal tubules with pyknotic nuclei. Hyaline debris detected in renal sections of combination group. Conclusion: Diet Coke and MSG induced degenerative changes in both the cerebellum and the kidney that was more significant in their combination. [ABSTRACT FROM AUTHOR]