Polycystic ovarian syndrome (PCOS) is a chronic disorder with a prevalence of 10% in women worldwide and its etiology still remains poorly understood. Insulin resistance is believed to be a main pathogenic factor involved in metabolic disturbances of PCOS. Butyrylcholinesterase (BuChE) has been shown to be linked with insulin resistance, type 2 diabetes and metabolic syndrome. Reduced activity of paraoxonase 1 (PON1) has also been reported in susceptibility to insulin resistance and the other metabolic diseases. It was to evaluate the enzymatic activity of BuChE, PON1 and their association with insulin resistance in PCOS women. In this case-control study, 56 PCOS women as the case group and 62 non-PCOS women as the control group were enrolled. Menstrual status, metabolic parameters such as fasting blood insulin (FINS), fasting blood sugar (FBS), homeostatic model assessment of insulin resistance (HOMA-IR), body mass index (BMI) was measured. Enzymatic activity of BuChE and PON1 was also measured. PCOS women had significantly higher menstrual irregularity (P=0.001), FINS (P=0.018), HOMA-IR (P=0.034) and BuChE activity (P=0.004) and lower PON1 activity (P = 0.006) than control. In PCOS women, BuChE was significantly correlated with BMI. In Insulin resistant women, BuChE activity was significantly higher in PCOS than control (P=0.012). No significant relationship was found between BuChE and PON1 activity in PCOS patients (P = 0.07). These results indicate that higher BuChE and lower PON1 activity are associated with pathogenesis of PCOS and insulin resistance could be a link for this connection.