Background: Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility in female. It is usually associated with insulin resistance (IR), obesity, hyperlipidemia, and type II diabetes. Irisin is amyokine which increases energy expenditure and protects against insulin resistance and obesity. There were controversial studies about the levels of irisin and its relation to hormonal and metabolic changes in PCOS. This study was designed to estimate serum level of irisin in letrozole-induced PCOS in both lean and obese female rats, and to study the link between serum irisin level and some metabolic and hormonal parameters in PCOS. Material and Methods: This study was conducted on 48 young virgin female of local strain albino rats. They were randomly divided into 2 equal groups: Group I: lean group were fed on normal laboratory chow diet and Group II: A high fat diet induced obesity group and each group was subdivided into group A (control) and group B (letrozole induced PCOS). Fasting serum irisin, Lutenizig hormone (LH), Folliclular stimulating hormone (FSH), testosterone, estradiol, progesterone, insulin, glucose, triglycerides, cholesterol, LDL and HDL levels were estimated. In addition, body mass index (BMI) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were calculated in all groups at the end of the experiment. Results: Serum irisin level was elevated in both lean and obese PCOS groups when compared to both lean and obese control groups. In addition, obese PCOS group had significant higher level of irisin when compared to lean PCOS group. Conclusion: Serum irisin level was positively correlated with BMI, HDL and testosterone levels and negatively correlated with HOMA-IR, insulin, cholesterol, triglycerides and LDL levels. Irisin may have a role in the development of polycystic ovary syndrome.