Objective: To investigate the relationship between myostatin serum levels and muscle mass, fat mass and HOMA before and after a 6-month lifestyle intervention program in obese children and adolescents. Design: A total of 57 overweight children and adolescents (female, n=27; age range, 6.0-16.1 years) were examined between 2007 and 2009. Mean BMI (+/- SD) was 31.1 (5.7) kg/m(2) corresponding to a mean BMI-SDSLMS of 2.2 (0.4). Muscle and fat mass were determined by means of DXA. Serum myostatin was measured by using a competitive ELISA. Results [mean SD]: After the 6-month intervention program, muscle mass (+2.1 +/- 2.7 kg, p<0.0001), and percentage myostatin serum levels (+23.7 +/- 26.7%, p<0.0001) were higher than before, whereas decreases in BMI (-0.4 kg/m(2)+/- 1.5, p<0.0001), fat mass (-1.2 +/- 3.9 kg, p<0.0001), and HOMA insulin sensitivity index (-0.78 +/- 3.28 SD, p=0.0004) were observed. In 86% (n=49, p<0.0001) of all cases, the intervention program resulted in a higher level of myostatin. After lifestyle intervention, patients with the greatest increase of myostatin had a significantly lower increase of muscle mass (p=0.048) but did not differ for fat mass. There was no significant correlation between Myostatin and HOMA insulin sensitivity index before and after lifestyle intervention. Conclusion: Both muscle mass and serum myostatin increased concordantly. Patients with the greatest rise of myostatin had a significantly lower increase of muscle mass suggesting a negative feedback loop between myostatin and muscle tissue. In our study, the change of myostatin serum levels was not associated with the amount of fat mass or HOMA insulin sensitivity index.