In order to preliminarily explore the correlation between the AMPK alpha-SIRT1 pathway and insulin resistance and reproductive function in PCOS mice and find the pathogenesis molecular mechanism and potential therapeutic target of PCOS, we carried out in vitro study of human granulosa KGN cells and in vivo study of PCOS mouse model which was constructed with DHEA, and AICAR and Compound C were applied. We have found that SIRT1 and AMPK alpha expression in KGN cells gradually decreased as DHEA concentration increased; Mice of the PCOS model were in an obvious status of IR (P < 0.05). Granulosa cells in their ovarian were present in fewer numbers and were disorderly arranged, their numbers of immature follicles were significantly increased, and their AMPK alpha-SIRT1 pathways were down-regulated. The AMPK alpha-SIRT1 pathway could be up-regulated after AICAR treatment, resulting in improved IR status (P < 0.0001); however, the abovementioned effect was blocked by Compound C. Thus we concluded that the AMPK alpha-SIRT1 molecular pathway may be a molecular mechanism of IR in PCOS and may serve as a therapeutic target for the development of potential treatments for improving metabolic and reproductive function in PCOS. (C) 2017 Elsevier Inc. All rights reserved.