Abstract Background PCOS appears to be associated with an increased risk of metabolic aberrations, including insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia, and cardiovascular disease throughout womens’ lifespan. Aim of the Work The aim of this study is to: Assess the association of Lipocalin-2 with polycystic ovary syndrome in a sample of the Egyptian female. Study the effect of metformin therapy on Lipocalin-2 level in female patients with polycystic ovary syndrome Patients and Methods Our study was conducted on 52 females. Their age ranged between 17-43 years old. They were collected from the outpatient obstetrics and gynaecology clinics of Ain Shams University Hospitals, assess the association of Lipocalin-2 with polycystic ovary syndrome in a sample of Egyptian females and its association with insulin resistance. It was conducted from June 2018 to March 2019. The study was explained to all patients and control subjects, and written consent was obtained before starting the study. Results Serum lipocalin-2 levels did not differ between patients with PCOS and BMI-matched healthy controls (P-value 0.193). In the present study, there was no significant difference between the 2 studied groups as regard HOMA-IR (p = 0.375). Metformin therapy for 3 months in patients with PCOS in the present study, resulted in significant reduction in lipocalin-2 level (p- value<0.01), (mean 54.2±15.3 ng/ml before metformin therapy vs 42.9±14.2 ng/ml after metformin therapy). In our study metformin therapy in PCOS group resulted in significant reduction in weight, BMI, waist circumference and HOMA-IR. Furthermore, linear regression analysis for the parameters affecting lipocalin level in our study, showed that BMI was the only significant confounder affecting lipocalin level. So the reduction in lipocalin level following metformin therapy in PCOS group in our study may be due to weight reduction perse. Conclusion In conclusion, our results show that PCOS per se is not associated with elevated serum lipocalin-2 levels. Weight loss induces a significant reduction in serum lipocalin-2 levels in overweight/obese patients with PCOS. Treatment with metformin of patients with PCOS also induces a reduction in serum lipocalin-2 levels.