Objective:To investigate circulating betatrophin levels in females with polycystic ovary syndrome(PCOS) and its correla-tion with insulin resistance(IR). Methods:Forty-four women with PCOS and thirty-five healthy women were recruited in a cross-sec-tional study. Serum concentrations of betatrophin was measured by enzyme-linked immunosorbent assay(ELISA). The correlation of betatrophin with IR and metabolic parameters was also analyzed. Then twenty-seven PCOS patients were studied longitudinally after three mouths of metformin and rosiglitazone sodium treatment. Results:Serum betatrophin levels were lower in PCOS patients than in healthy control subjects(0.43±0.15) ng/mL vs. (1.17±0.57) ng/mL,P=0.000. Serum betatrophin negatively correlated with fasting plasma glucose(FPG),2h postprandial plasma glucose(2hPG),fasting insulin(FINS),homeostatic model assessment insulin resistance(HOMA-IR),high-sensitivity C-reactive protein (hs-CRP),even after controlling for age and body mass index(BMI) in PCOS par-ticipants(r=-0.331,r=-0.372,r=-0.311,r=-0.337,r=-0.338,all P<0.05). Moreover,stepwise multiple regression analysis showed that HOMA-IR was independently related to betatrophin in PCOS subjects(P<0.05). After rosiglitazone sodium and metformin treatment,PCOS patients showed higher betatrophin concentrations than its baseline levels(0.87±0.51) ng/mL vs. (0.42±0.17) ng/mL,P=0.000. Conclusion:Circulating betatrophin levels are de-creased in patients with PCOS,and associated with IR.