Background: Exercise training plays an important role in combating Alzheimer's disease. Present study aimed to investigate the effect of 12 weeks aerobic training on the levels of tumor necrosis factor alpha (TNF-α) in the hippocampus and prefrontal cortex, and also depression in rats with Alzheimer's disease. Methods: The 40 Wistar rats were divided into four equal groups including saline (S), saline +training (ST), training +STZ (AT) and STZ (A). Alzheimer's was induced by injection of 3 mg/kg streptozotocin (STZ) into the ventricles of brain. The aerobic training program (each session lasted 30 minutes with 10-12 meters per minute speed) performed for 12 weeks and five sessions per week on a treadmill. The 48 hours after last training session, brain tissue (hippocampal and prefrontal cortex areas) was removed and TNF-α levels were measured by ELISA method. Data were evaluated using the statistical method of analysis of variance at a significant level (P <0.05). Result: TNF-α levels in the hippocampus were significantly higher in group A compared to S (p= 0.010), ST (p= 0.014) and AT (p= 0.041) groups. Moreover, no significant change was observed for TNF-α levels in prefrontal cortex in different groups (p= 0.276). In addition, a significant increase in inactivity duration (FST) was observed in group A compared to other groups (p <0.05) and also a significant decrease in sucrose preference (SPT) was observed in group A compared to other groups. (p<0.05). Conclusion: The present study findings indicated that, the positive effects of aerobic training in rats with Alzheimer's disease are exerted partly by modulating the levels of inflammatory factors such as TNF-α in the brain especially the hippocampus. پرونده مقاله