Abstract: Insulin resistance(IR) is the main feature of type 2 diabetes mellitus (T2DM). Although the molecular mechanisms of IR have been well understood in the past, many regulatory details of the mechanisms leading to IR are still unclear, especially the regulatory role of epigenetics in IR. This article reviewed the important role of various forms of acetylation in regulating insulin signal transduction and glucose metabolism from two aspects of signal pathway and environmental homeostasis. Although the understanding of acetylation was not comprehensive, these theoretical knowledge would help to improve the understanding of the pathogenesis of diabetes, thus providing a theoretical basis for the development of more effective methods to treat diabetes.