Background and Objective: Betatrophin, a novel hormone, is correlated with insulin resistance and promotes pancreatic beta- cell growth in mice. The aim of this study was to determine circulating betatrophin levels in overweight or obese children and adolescents. Methods: The following pairs of subjects were included: ( i) normal- weight healthy ( n= 27) and overweight or obese ( n= 28); ( ii) non- insulin- resistant overweight or obese ( n= 25) and insulin- resistant obese ( n= 15); ( iii) normal- weight males ( n= 18) and females ( n= 20); ( 4) 5 to 8 yr olds ( n= 20) and 8 to 14 yr olds ( n= 18). Circulating betatrophin levels were measured using enzyme- linked immunosorbent assay ( ELISA). In addition, clinical data were recorded and anthropometrical measurements were performed. Results: Circulating betatrophin levels were increased significantly in obese children and adolescents with insulin resistance ( 365.77 +/- 30.86 pg/ mL) compared with overweight or obese subjects without insulin resistance ( 274.25 +/- 26.52 pg/ mL; p< 0.05). However, no differences in betatrophin levels were seen between lean and overweight or obese children ( 323.18 +/- 25.91 vs. 348.27 +/- 18.91 pg/ mL, respectively; p> 0.05). In the normal- weight cohort, males had higher serum betatrophin level than did females, and subjects < 8 yr old had lower serum betatrophin levels compared with those > 8 yr. Surprisingly, betatrophin concentrations were correlated negatively with body mass index ( BMI), but not with the BMI Z- score, in non- insulin- resistant children and adolescents. Conclusions: These results demonstrated that circulating betatrophin levels were increased in insulin- resistant obese children or adolescents and might act as a potential biomarker of insulin resistance in these populations. Furthermore, serum betatrophin concentrations might vary during the development of children and adolescents, as well as between genders.