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Introduction: Using deep frying oil (DFO) in preparing various foods. High temperature alter the constituents of DFO, which mav be harmful for different cells, paerticularly neural cells.  It seems that physical activity and phytochemical compounds can reduce the negative effects of consuming DFO. However, their definite effect is not known. The aim of this study was to determine the effect of aerobic exercise and octopamine on gene expression of dopamine, serotonin, norepinephrine, 5-HT, and dopamine, as well as the number of Purkinje cells and the percentage of apoptotic cells in the cerebellum of rats fed with DFO. Materials and Methods: Thirty male Wistar rats with a mean age of 20 weeks and weight of 300-350 g were divided into five groups: healthy control, DFO, DFO + exercise, DFO + octopamine, and DFO + exercise + octopamine. At the beginning of the first week, rats were fed with DFO. The rats received the intraperitoneal injection of octopamine for 4 weeks, 5 days per week.  The training was done for 4 weeks, 5 days a week, and 20 minutes per day at a speed of 26 m/minute aerobic exercises. After 4 weeks, chemical analyzes were performed by Real-time PCR to measure gene expression and Western blot to measure protein expression on samples fixed cerebellum. Results: The results showed that DFO uptake significantly decreased the expression of dopamine, serotonin, norepinephrine, 5-HT, dopamine, and cerebellar Purkinje cells and increased the percentage of apoptotic cells. Octopamine intake or exercise increased the expression of dopamine, serotonin, norepinephrine, 5-HT, dopamine, and the number of Purkinje cells and decreased the percentage of apoptotic cells. The co-application of  of octopamine and exercise had no significant effect on increasing the expression of dopamine, serotonin, norepinephrine, 5-HT, dopamine protein, and number of Purkinje cells, but significantly reduced the percentage of apoptotic cells. Conclusion: Consumption of high-fat food disrupts dopaminergic and serotonergic pathways. Aerobic exercise and octopamine protective effect against DFO toxic effects on cerebellum tissue.