Asprosin an adipokine, is induced by fasting and targets the liver, promoting hepatic glucose release. Asprosin hormone level was found to be changed with insulin resistance. Moreover, there is an association between autoimmune thyroiditis and PCOS with insulin resistance. Metformin treatment and exercise training have been shown to be an effective treatment as insulin sensitizers. Aim of the study: To study the changes in thyroid function and serum asprosin level in letrozole-induced PCOS in rats, and, to investigate the effect of moderate exercise training and metformin treatment on those changes. Materials and Methods: 52 female adult albino rats were divided randomly and equally into 4 groups [control, polycystic ovary syndrome (PCOS), PCOS+ practiced exercise and PCOS+ practiced exercise+ Metformin treated]. In Control group, rats were given 1% aqueous solution of carboxy methyl cellulose (CMC) orally once daily for 11 weeks (study duration). In PCOS group, rats were administered letrozole at concentrations of 1 mg/kg BW dissolved in 1% CMC (1 ml/kg) orally once daily for 11 weeks. In PCOS+ practiced exercise group, letrozole was given as in PCOS group and the rats practiced moderate swimming training (5 days/week, for the last 8 weeks). In PCOS+ practiced exercise+ Metformin treated group, letrozole was given as in PCOS group and rats practiced exercise as in PCOS + exercise group and were given additionally metformin (50 mg/100 g BW in 0.05 ml of distilled water) orally once daily for the last 8 weeks. Serum was separated from collected blood at the end of experiment for measurement of asprosin, TSH, T3, T4, FSH, LH, estradiol, progesterone, testosterone, glucose, insulin, triglyceride, cholesterol, HDL, SOD, TNF-α and IL-6 levels. Ovarian and thyroid histopathological study were done. Results: Moderate swimming exercise and metformin treatment resulted in a significant reduction in BMI and serum levels of asprosin, glucose, insulin, testosterone, LH, lipid profile and inflammatory cytokines, with a significant increase in serum levels of FSH, estradiol, progesterone and SOD in comparison to rats with PCOS. In addition to restoration of the thyroid functions by TSH- lowering effect in those rats to become nearly normal. Conclusion: Letrozole-induced PCOS disturbs thyroid function and affects asprosin serum levels. Both moderate exercise training and metformin treatment have insulin sensitizing effects and thus, they could modulate disturbances in thyroid function, and in serum levels of asprosin, sex hormones, inflammatory cytokines and antioxidants.