BACKGROUND: One of the mechanisms by which exercise training exerts its anti-inflammatory effects against obesity-induced inflammation is the secretion of proteins called myokines from skeletal muscles. So, this study aimed at investigating the effect of a 6-weeks running sprint interval training (R-SIT) protocol on serum level of meteorin-like (Metrnl) hormone, insulin resistance index and body composition in sedentary overweight adolescent boys. METHODS: Twenty overweight adolescent boys (aged: 18.0±1.5 years, weight: 81.8±4.3 kg, BMI: 27.6±0.8 kg/m2) voluntarily participated in this study. The subjects were randomly assigned into two groups of control (CG, N.=10) and training (TG, N.=10). Subjects in training group performed their training 3 days/week for six weeks and CG did their daily routine activities. Anthropometrics parameters and fasting serum insulin, glucose, and Metrnl levels were measured at the baseline and at the end of the study. Insulin resistance was considered as HOMA-IR. RESULTS: Training increased significantly fasting serum level of Metrnl hormone and reduced significantly body weight (BW), body mass index (BMI), body fat PERCENTAGE (BF%), HOMA-IR, fasting serum levels of glucose, insulin of sedentary overweight adolescent boys. However, no correlations were found between changes of serum Metrnl and changes of body weight, BMI, BF%, serum glucose, insulin and HOMA-IR in overweight adolescent. CONCLUSIONS: The increased fasting serum level of Metrnl hormone after 6 weeks of R-SIT might be attributed to the anti-inflammatory effects of R-SIT on metabolic regulation, which was accompanied by improved HOMA-IR and body composition within sedentary overweight adolescent boys.