International Journal of Preventive Medicine (Int J Prev Med)2008-780212102022010225492549ENInternational Division, Shiraz University, ShirazDepartment of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, TehranDepartment of Sport Sciences, School of Education and Psychology, Shiraz University, Shiraz20211229Background: The effect of exercise on the cerebellum cells in diabetic‑induced neuropathy and healthy situations is not clear yet. Growth‑associated protein 43 (GAP‑43) and adenylyl cyclase‑associated protein 1 (CAP‑1) proteins can restore nerve cells. This study aimed to investigate the effect of aerobic exercise on GAP‑43 and CAP‑1 and their mRNA in the cerebellar tissue of diabetic‑induced neuropathy and healthy Wistar rats. Methods: Around 40 healthy male Wistar rats with a mean weight of 271 ± 11.2 g were divided randomly into four groups; healthy aerobic exercise, diabetic‑aerobic exercise, healthy‑control, and diabetic‑control. The exercise group performed aerobic exercise 5 days per week for 6 weeks. Results: Exercise increased CAP1 protein in the cerebellum tissue of healthy (P = 0.002) and diabetic (P = 0.002) groups compared with matched control groups. The effect of exercise on CAP1 was greater in diabetic compared with the healthy group (P = 0.002). The expression of CAP1 mRNA in the cerebellum was higher in the healthy exercise compared with the healthy control group (P = 0.002) and in the healthy exercise compared with the diabetic exercise group (P = 0.026). GAP43 protein was lower in the healthy exercise compared with the healthy control group (P = 0.002) while it was higher in diabetic exercise compared to the healthy exercise group (P = 0.002). Expression of GAP43 mRNA in the cerebellum was higher in the healthy (P = 0.002) and diabetic (P = 0.002) exercise groups compared to non‑exercise matched groups and in the diabetic control group compared with the healthy control group (P = 0.002). Exercise improved latency in diabetic (P = 0.001) and healthy exercise groups (P = 0.02). No significant difference was found in blood glucose between exercise and control groups (P > 0.05). Conclusion: Exercise improved cerebellar functions in healthy and diabetic rats, probably mediating by CAP1 protein, even without changing blood glucose.http://ijpm.mui.ac.ir/index.php/ijpm/article/view/2549http://ijpm.mui.ac.ir/index.php/ijpm/article/download/2549/717718388