Introduction: Increasing the expression of FOXO1 gen in hippocampus as well as inflammatory factor of TNF-α,in diabetic individual's causes the expression of genes involved in apoptosis and disrupts its performance. The aim of the present study was investigation of the effect of 6-weeks HIIT on FOXO1 gene expression in the hippocampus and level of serum TNF-α,in male Wistar diabetic rats. Materials and Methods: For this study, 48 male Wistar rats (4 weeks old) with 150±, 10 g weight were categorized in 4 groups of (n=12): diabetic rats, exercise diabetic, control and exercise control. For induction of diabetes, peritoneal injection of STZ solution (50 mg/kg) was used. After a week of familiarization with the environment and practice, HIIT protocol consisted of 3 days per week for 6 weeks with 50% to 110% of maximum oxygen consumption was performed. 24 hours after the completion of the exercise, the functional test was taken and the animals were autopsy 48 hours after the functional test. FOXO1 gene expression was evaluated using Real Time PCR technique. Results: Regarding the results, HIIT significantly decreased FOXO1 gene expression in training groups (P≤, 0. 01). Also, TNF-α,protein decreased significantly (P≤, 0/05). Weight gain of the hippocampus was associated with a reduction in the FOXO1 gene in the diabetic training group. Conclusion: HIIT probably reduce the weight loss of the hippocampal tissue that caused by diabetes, by reducing the FOXO1 apoptotic and inflammatory factors of TNF-α, .