Introduction: Research has shown that various exercises may have different effects on serum levels of brain-derived neurotrophic factor (BDNF). However, there is little information on the interactive effect of intense interval exercises through the effect on weight, body mass index, and waist to hip on BDNF. Hence, the purpose of the present study was to investigate the effect of 6 weeks of high-intensity interval training on serum levels of brain-derived neurotrophic factor and body composition of inactive male students. Materials and Methods: In this quasi-experimental study, 16 non-athlete male students from Sistan and Baluchestan University were divided into two groups of 8 as control and training through simple randomization. The training group, performed 6 weeks of high-intensity interval training, in a 20-meter shuttle run for 30 seconds with a 90 percent maximum heart rate and 30 seconds active rest between each repetition was performed. The control group did not perform activity. BDNF values were measured 24 hours before and 48 hours after the first and last training sessions of exercise using ELISA method by commercial kits. Data were analyzed using independent t-test and t-paired test at p≤ 0. 05level. Results: In the present study, the findings showed that after 6 weeks, weight (p = 0. 008) and body mass index (p = 0. 005), decreased in high-intensity interval training group compared to control one, which was consistent with a significant increase in serum levels of BDNF (p = 0. 031). While, none of the variables significantly changed in control group (p>0. 05), in addition, there was a significant increase in serum contents of BDNF in HIIT group compared to control (p = 0. 002). Conclusion: Regarding the parameters of study, it can be concluded that high-intensity interval training improve BDNF through reduction in weight and BMI in inactive male students.