To evaluate the effect of metformin therapy for more than three months on serum ghrelin and adiponectin level and to assess the relationship between them with insulin resistance parameters in obese patients with polycystic ovary syndrome (PCOS). A case-control study design was adopted in the Fertility and In Vitro Fertilization (IVF) Center at AL. Batool Teaching Hospital Mosul City/ Iraq, in the period between 1st of November 2013 and 1st of May 2014. This study included a group of 41 obese women with PCOS of reproductive age who used metformin for more than three months (metformin users) with another age-and body mass index (BMI)- matched group of 44 obese women with PCOS who did not use metformin (metformin non-users and served as control). A 10 ml of fasting venous blood sample was taken from each PCOS woman of the two groups. The sera were used to measure serum ghrelin, adiponectin, insulin and fasting serum glucose (FSG) level by using commercially specific kits, whereas; BMI and insulin resistance represented by Homeostasis Model Assessment (HOMA) was calculated by using especial equations. The results of this study revealed that there were no significant differences in the mean BMI, waist to hip ratio (WHR), serum ghrelin, FSG and fasting serum insulin (FSI) and HOMA-IR between the metformin users in comparison with metformin non-users obese PCOS patients groups. This study found that there was a significant higher mean serum adiponectin level of the obese metformin users in comparison with the obese metformin non-users PCOS patients. There was a significant positive correlation between BMI and insulin level, BMI and HOMA-IR and between FSG level and HOMA-IR. Also there were a very high significant positive correlation between insulin level and HOMA-IR. In conclusions, metformin therapy for more than three months in obese PCOS patients was associated with a significant higher mean serum adiponectin level than in metformin non-users group. There were non-significant changes in the mean FSG, serum ghrelin level and insulin resistance parameters. Also there were no significant correlation between neither mean serum ghrelin nor adiponectin with the insulin resistance and anthropometric parameters.