Abstract Background: The cerebellum means the little brain which located behind the big brain. It was involvedin different functions like cognition, memory and motor activity. Meth-otrexate is anti-cancer drug widely used in chemotherapy regimens. Also, it was used as an anti-inflammatory drug. Methotrexate has serious side effects on the nervous system. Vitamin C is the most common antioxidant element; it acts as a free radical scavenger especially in the nervous tissue. Aim of Study: The aim is to identify the serious toxic effect on the fine cellular structure of the cerebellar cortex of albino rats, and to determine if vitamin C can protect against serious of methotrexate or not. Material and Methods: We used fifteen male albino rats and they were divided in to three groups. First group considered as control, the second received 10mg/kg by intraperitoneal injection as single dose weekly for four weeks. The third group received the same methotrexate dose and vitamin C as 20mg/kg through the intragastric tube every other day for four weeks. After one month of the experiments, rats were decapitated and brains were extracted and cerebella are separated and cut for different serial sagittal sections, they were processed for electron microscopic study. Results: Exposure to methotrexate resulted in pathological changes at cellular component of cerebellar cortex in the form shrinkage of Purkinje cell, karyolitic changes in granule cells and nuclear damage was viewed and photographed by the electron microscope, but when vitamin C was administrated at the same time, these changes were decreased within Purkinje and granule cells. Conclusion: Methotrexate is asharmful drug, it destroys the cortex oh cerebellum, but when vitamin C is administrated with it, it can diminish its harmful effect.