This study investigates the impact of different exercise intensities on cerebral BDNF levels and the role of FNDC5/Irisin. Wistar rats were divided into four groups based on their exercise intensity: sedentary (SED), low- (40% of maximal aerobic speed, MAS), intermediate- (50% MAS), and high- (70% MAS) intensity treadmill exercise. The soleus (SOL) and gastrocnemius (GAS) muscles were analyzed for FNDC5 and hippocampal BDNF expressions, and serum/hippocampal irisin levels were measured. Key findings include: 1. **Cerebral BDNF Levels**: Serum irisin and hippocampal BDNF levels vary with exercise intensity, showing a threshold intensity at 50% MAS. 2. **Correlation with BDNF**: Hippocampal BDNF levels positively correlate with serum irisin but not with hippocampal FNDC5/Irisin. 3. **FNDC5/Irisin Expression**: Gas muscle overexpresses FNDC5/Irisin in type II muscle fibers in response to exercise intensity, while SOL muscle does not show significant changes. 4. **Correlation with Serum Irisin**: FNDC5/Irisin expression in GAS muscle is positively correlated with serum irisin levels. The study suggests that peripheral FNDC5/Irisin levels likely explain the exercise-dependent hippocampal BDNF expression, highlighting the importance of muscles with fast-twitch fibers in the exercise-induced increase in BDNF. These findings have implications for understanding the mechanisms of exercise-induced cognitive enhancement and the potential use of irisin as a peripheral marker for cognitive function.This study investigates the impact of different exercise intensities on cerebral BDNF levels and the role of FNDC5/Irisin. Wistar rats were divided into four groups based on their exercise intensity: sedentary (SED), low- (40% of maximal aerobic speed, MAS), intermediate- (50% MAS), and high- (70% MAS) intensity treadmill exercise. The soleus (SOL) and gastrocnemius (GAS) muscles were analyzed for FNDC5 and hippocampal BDNF expressions, and serum/hippocampal irisin levels were measured. Key findings include: 1. **Cerebral BDNF Levels**: Serum irisin and hippocampal BDNF levels vary with exercise intensity, showing a threshold intensity at 50% MAS. 2. **Correlation with BDNF**: Hippocampal BDNF levels positively correlate with serum irisin but not with hippocampal FNDC5/Irisin. 3. **FNDC5/Irisin Expression**: Gas muscle overexpresses FNDC5/Irisin in type II muscle fibers in response to exercise intensity, while SOL muscle does not show significant changes. 4. **Correlation with Serum Irisin**: FNDC5/Irisin expression in GAS muscle is positively correlated with serum irisin levels. The study suggests that peripheral FNDC5/Irisin levels likely explain the exercise-dependent hippocampal BDNF expression, highlighting the importance of muscles with fast-twitch fibers in the exercise-induced increase in BDNF. These findings have implications for understanding the mechanisms of exercise-induced cognitive enhancement and the potential use of irisin as a peripheral marker for cognitive function.