Proteomic analysis of skeletal muscle in exercise-trained, insulin-resistant mice has revealed alterations in the levels of Topiramate abundance of proteins involved in molecular chaperoning, anti-oxidative stress response and mitochondrial functions. Because F Protopine causes progressive degeneration of the structure and function of the skeletal muscles, it likely affects many proteins and enzymatic systems. However, the proteomic profile of skeletal muscle in animals with streptozotocin-induced diabetes and chronic exposure to F has not been investigated. We hypothesize that upon chronic exposure to F, rats with streptozotocin-induced diabetes will display significant alterations in the levels of skeletal muscle proteins involved in IR. Therefore, the aim of this study is to describe the global changes in the profile of protein abundance that occurs in rats with streptozotocin-induced diabetes and chronic exposure to varying concentrations of F introduced through the drinking water. To the best of our knowledge, this is the first study examining the effects of F provided through drinking water on rats with streptozotocin-induced diabetes. Previous studies have treated the animals with F for 6 weeks; however, a pilot study revealed high levels of mortality prior to completion of the experimental period. Therefore, an experimental time of 22 days was selected. The tested F concentrations, which were administered via drinking water, were designed to correspond to 1 ppm F and 5 ppm F. These concentrations had to be modified because rats metabolize F approximately ten times faster than humans. The total number of protein spots identified in the muscle under the different conditions was similar to that observed for the same type of tissue in other studies. Proteomic analyses reveal that the largest differences in expression, between ND vs. D rats with no exposure to F, occurred in genes related to muscle contraction. D rats displayed an increased expression of many types of myosin proteins. The muscles of diabetic animals regularly need repair, which requires a higher concentration of contractile proteins.