Background: Polycystic ovary syndrome (PCOS) is a complex reproductiveendocrine-metabolic disorder and insulin resistance (IR) is a common feature of it.Objective: To clarify the pathophysiological mechanisms of POCS, highlight its basicrelationship with IR and to investigate the efficacy of metformin therapy and ovariandrilling in these cases. Patients and Methods: Thirty two PCOS patients (sixteenreceived metformin 850 mg twice daily for four months[group 1] and sixteenunderwent laparoscopic ovarian drilling [group 2]) and fifteen healthy controls wereincluded in this study. Body mass index (BMI) evaluation followed by ultrasoundexamination for measurement of antral follicles count (AFC) in both ovaries, oralglucose tolerance curve, fasting blood glucose, insulin and glucose / insulin ratio(G/I) were measured in addition to serum total testosterone (T), leutinizing hormone(LH) and insulin like growth factor-1 (IGF-1) for all subjects. These parameters werereevaluated again 4 months after either types of treatment. Results: PCOS patientshad significant increase BMI, T, LH, IGF-1, fasting blood glucose, insulin level andAFC but G/I ratio was significantly lower. Significant negative correlations betweenfasting G/I ratio and either of BMI, T, and AFC respectively were evident. Impairedfasting glucose level at baseline was observed in PCOS patients while after metforminand laparoscopic drilling it was significantly improved. Metformin significantlydecreased BMI, serum T, LH levels, IGF-1 and AFC and increased the G/I ratioversus pretreatment values. Also, ovarian drilling has similar but less obvious effects.Conclusion: IR plays a vital pathophysiological role in PCOS patients as manifestedby causal relationship between insulin resistance and metabolic and reproductivechanges of PCOS. Metformin and ovarian drilling potentially improve these changes.