Reactive oxygen species (ROS) have emerged as intracellular messengers participating in both physiological and pathological adaptations in skeletal muscle. Physical activity is well known to increase ROS production in muscle and a major mode of regulation of protein function occurs through production of reactive oxygen species (ROS) and related species that selectively and reversibly induce covalent modification of cysteine residues in proteins, a process referred to as redox signaling. One of the health benefits of exercise is an increase in insulin sensitivity and the molecular underpinnings are not fully understood but might involve redox modification of proteins involved in insulin action. I will describe the redox proteomics signature of cysteines in human muscle following a single bout of exercise. I will also show the cysteine oxidation profile of muscle during insulin stimulation in the post-exercise period and how it relates to increased insulin sensitivity of muscle glucose uptake in humans.