This study investigates the impact of exercise intensity on cerebral brain-derived neurotrophic factor (BDNF) levels and the role of FNDC5/Irisin. Wistar rats were divided into four groups based on exercise intensity: sedentary (SED), low (40% of maximal aerobic speed, MAS), intermediate (50% of MAS), and high (70% of MAS). The study evaluated the expression of FNDC5 and BDNF in soleus (SOL) and gastrocnemius (GAS) muscles, as well as hippocampal BDNF and serum/hippocampal irisin levels. Key findings include: (1) serum irisin and hippocampal BDNF levels vary with exercise intensity, with a threshold at 50% of MAS; (2) hippocampal BDNF levels positively correlate with serum irisin but not with hippocampal FNDC5/Irisin; and (3) GAS muscles overexpress FNDC5/Irisin in type II fibers in response to exercise intensity. These results suggest that peripheral FNDC5/Irisin levels likely explain exercise-dependent hippocampal BDNF expression. The study also found that FNDC5/Irisin expression in GAS muscles increased with exercise intensity, particularly in type II fibers, and that this expression correlated with serum irisin levels. In contrast, FNDC5/Irisin expression in the hippocampus was not significantly affected by exercise intensity. The results indicate that the expression of FNDC5/Irisin in skeletal muscles, particularly in type II fibers, plays a key role in the regulation of BDNF levels in the brain. The study highlights the importance of muscle fiber type in the regulation of irisin and BDNF, suggesting that muscles with a higher proportion of type II fibers may be more effective in promoting cognitive benefits through exercise. The findings have implications for understanding the mechanisms underlying the cognitive benefits of exercise and could inform the development of exercise protocols aimed at enhancing cognitive function.This study investigates the impact of exercise intensity on cerebral brain-derived neurotrophic factor (BDNF) levels and the role of FNDC5/Irisin. Wistar rats were divided into four groups based on exercise intensity: sedentary (SED), low (40% of maximal aerobic speed, MAS), intermediate (50% of MAS), and high (70% of MAS). The study evaluated the expression of FNDC5 and BDNF in soleus (SOL) and gastrocnemius (GAS) muscles, as well as hippocampal BDNF and serum/hippocampal irisin levels. Key findings include: (1) serum irisin and hippocampal BDNF levels vary with exercise intensity, with a threshold at 50% of MAS; (2) hippocampal BDNF levels positively correlate with serum irisin but not with hippocampal FNDC5/Irisin; and (3) GAS muscles overexpress FNDC5/Irisin in type II fibers in response to exercise intensity. These results suggest that peripheral FNDC5/Irisin levels likely explain exercise-dependent hippocampal BDNF expression. The study also found that FNDC5/Irisin expression in GAS muscles increased with exercise intensity, particularly in type II fibers, and that this expression correlated with serum irisin levels. In contrast, FNDC5/Irisin expression in the hippocampus was not significantly affected by exercise intensity. The results indicate that the expression of FNDC5/Irisin in skeletal muscles, particularly in type II fibers, plays a key role in the regulation of BDNF levels in the brain. The study highlights the importance of muscle fiber type in the regulation of irisin and BDNF, suggesting that muscles with a higher proportion of type II fibers may be more effective in promoting cognitive benefits through exercise. The findings have implications for understanding the mechanisms underlying the cognitive benefits of exercise and could inform the development of exercise protocols aimed at enhancing cognitive function.