Insulin resistance in skeletal muscle is established as an early and key event in the pathogenesis of Type 2 Diabetes and contributes to whole body hyperinsulinemia and hyperglycemia. During normal conditions, glucose is taken up into skeletal muscle when glucose transporter (GLUT) 4 translocates to the plasma membrane in response to stimuli such as insulin and muscle contraction. Contraction-stimulated glucose uptake is not affected by insulin resistance, likely because the intracellular events that regulate GLUT4 translocation by insulin and muscle contraction are distinct. Because of this, activation of glucose uptake by exercise is an important alternative way to maintain whole body glucose homeostasis in insulin resistant states such as Type 2 Diabetes.Rac1 is a small GTPase that regulates the actin cytoskeleton in cultured muscle cells. We have found that Rac1 can be activated by both insulin and muscle contraction in mouse and human skeletal muscle. We identify Rac1 as an important regulator of muscle glucose uptake because pharmacological inhibition as well as knockout of Rac1 reduces insulin- and contraction-stimulated glucose uptake. Rac1 knockout mice display significantly reduced glucose transport in response to ex vivo electrically-induced contraction in isolated skeletal muscle. In vivo treadmill running-induced glucose uptake was also significantly reduced in Rac1 knockout mice despite similar exercise performance and similar activation of AMPK. We also have found that Rac1 is activated by passive stretching (a major component of the contraction stimuli) and that stretch-stimulated glucose transport is reduced in muscles of Rac1 knockout mice. These findings suggest that Rac1 may signal to glucose transport during contractions via stretch-activated pathways. Our findings thus identify Rac1 as a novel convergence point between insulin and contraction-signaling to glucose uptake in skeletal muscle.