Insulin resistance is a key feature of Type 2 diabetes and an important therapeutic target to address glycemic control to prevent diabetic complications. Lifestyle advice is the first step in the ADA/EASD consensus guidelines followed by metformin therapy. Aerobic exercise (AE) can increase insulin sensitivity by several molecular pathways including upregulation of insulin transporters in the cellular membrane of insulin-dependent cells. In addition, AE improves insulin sensitivity by amelioration of the pathophysiologic pathways involved in insulin resistance such as the reduction of adipokines, inflammatory and oxidative stress responses, and improvement of insulin signal transduction via different molecular pathways. This review details the molecular pathways by which AE induces beneficial effects on insulin resistance.© 2019 Wiley Periodicals, Inc.