Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting female reproductive life. PCOS is multifaceted disorder and to date there is no defined cause or therapy. Several causes were implied as being contributing factors in the mechanism of this disease including hyperandrogenism, insulin resistance, obesity and chronic inflammation.In this study insulin resistance is considered as one of the main pathogenesis in letrozole induced animal model of polycystic ovary, so treatment of insulin resistance by different drug regimen will be helpful in the treatment of PCOS and its complications. Methods: Twenty female albino rats were divided into two groups 10 rats each; the control group (received the vehicle) and the PCO group received letrozole (1 mg/kg/ day) dissolved in 1% carboxymethyl cellulose orally for five weeks. Ovaries and serum were harvested and studied biochemically, histologically and immunohistochemically. Results: Biochemical analysis showed a significant increase in serum testosterone and insulin hormones and HOMA-IR and in tissues A type fatty acid binding protein (A-FABP). Conclusion: AMPK upregulation in PCO group could implicate it in pathogenesis of PCOS.