Background: Proliferation of adipose tissue increases leptin secretion and decreases adiponectin concentration. Exercise is an intervention to control and reverse this process. Therefore, the present study aimed to determine the effect of 8-week high-intensity interval training on leptin, adiponectin, and the ratio of leptin to adiponectin in overweight adolescent boys. Materials and Methods: The present quasi-experimental study was conducted on overweight adolescent boys (13-18 years old, mean body mass index 27.05±1.4 kg/m2). A total of 30 participants volunteered who were divided into three groups of 10 people including short-term (9 sessions of 30-second training with 150-second rest), long-term (4 sessions of 150-second training with 240-second rest), and control group. The training groups performed high-intensity running sprints 3 times per week for 8 weeks. Data were analyzed using two-way repeated-measures ANOVA (3 groups×2 measurement times) and Bonferroni test. Results: Performed high-intensity interval training failed to affect leptin, weight, and body mass index but increased adiponectin and decreased the ratio of leptin to adiponectin (P = 0.042) and fat percentage. No difference was observed between the two types of interval training in changing the level of leptin, adiponectin, fat percentage, and body mass index. Conclusion: High-intensity interval training increases metabolic benefits in overweight adolescents by increasing adiponectin and subsequently decreasing the leptin/adiponectin ratio. Low exercise, no calorie restriction, and other factors affecting puberty may influence the research results.