Background: Polycystic ovary syndrome (PCOS) is a very common problem in reproductive age; Obesity and insulin resistance (IR) play critical roles in its etiology. Limited studies have investigated the link between nesfatin-1 levels and PCOS. However, these studies are controversial. Objectives: This study aimed to evaluate possible changes of serum nesfatin-1 Levels in letrozole-induced PCOS in lean and obese rats, and its association with some hormonal and metabolic parameters. Material and methods: Forty two young virgin healthy female albino rats were used. Rats were divided into three equal groups: Group I (control), group II (lean PCOS) rats fed ordinary rodent diet for 9 weeks, and then received a daily single dose of letrozole orally (0.5 mg/kg/BW) for 21 days. Group III (obese PCOS) rats fed high fat diet for 9 weeks, and then received a daily single dose of letrozole (0.5 mg/kg/BW) orally for 21 consecutive days. At the end of experiment, serum levels of Nesfatin-1, free testosterone, LH, FSH, estradiol, progesterone, glucose and insulin were detected. BMI and HOMA-IR were calculated. Ovarian histopathology was done. Results: In obese polycystic ovary group, serum nesfatin-1 level was significantly lower and accompanied by significant hyperinsulinemia, hyperglycemia, insulin resistance, and high BMI when compared to both of lean polycystic and control groups. Moreover, serum nesfatin-1 level significantly negative correlated with serum insulin levels, serum glucose levels, HOMA-IR, and BMI, but correlated positively with LH levels. In lean polycystic group, serum nesfatin-1 level did not significantly change, when compared to control group, In addition, there was an absence of any significant change in serum insulin levels, serum glucose levels, HOMA-IR, or BMI. Conclusion: Serum nesfatin-1 level seemed to be related to several metabolic syndrome parameters rather than to polycystic ovary syndrome. Our findings raised a possibility that nesfatin-1 level played some role in PCOS. Therefore, larger scale and more detailed molecular studies in vivo and vitro on ovarian function are needed.