Background: The consumption of fast- food is increasing among children, adolescents and adults. Carbonated drinks as Diet Coke are widely consumed with fast food. 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 of adult male albino rats.Materials and Methods: Forty adult male albino rats were divided into four groups. Group I: control group. Group II (Diet Coke group) which was subdivided into: subgroup IIA: each rat received 2.5 ml of Diet Coke twice daily by oral gavage and subgroup IIB: rats received Diet Coke instead of water throughout the day. Group III (MSG group): rats received MSG salt solution (3 gm MSG / kgm) by oral gavage once daily. Group IV (combination group) rats received combination of MSG solution and Diet Coke. This group was subdivided into two subgroups. Subgroup IVA: rats received MSG salt solution in the same dose as group III and 2.5 ml of Diet Coke twice daily, by oral gavage. Subgroup IVB: rats received MSG salt solution in the same dose as group III and Diet Coke instead of water throughout the day. At the end of the experiment (21 days) cerebella were dissected out and processed for histological, immunohistochemical and morphometric studies. Results: Histological examination of the cerebellar cortex revealed that both Diet Coke and MSG either separately or in combination resulted in degenerative changes that were more significant in the combination group.Conclusion: Diet Coke and MSG induced degenerative changes in the cerebellar cortex that was more significant in their combination.