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Exercise training alters protein abundance in the muscle of healthy individuals, but the effect of exercise on these proteins in patients with type 2 diabetes (T2D) is unknown. The aim of this study was to determine how exercise training alters the skeletal muscle proteome in patients with T2D.Biopsies of the vastus lateralis were obtained before and after 4 wk of exercise training in six patients with T2D (54 ± 4 yr; body mass index (BMI), 29 ± 2) and six age- and BMI-matched control subjects (48 ± 2; BMI, 28 ± 3) studied at the baseline. The proteins were identified and quantified using normalized spectral abundance factors by multidimensional high-resolution mass spectrometry.Of the 1329 proteins assigned at the baseline, 438 were present in at least half of all the muscle samples; of these, 15 proteins differed significantly between the patients with T2D and control subjects (P < 0.05). In the diabetic patients, the exercise training altered the abundance of 17 proteins (P < 0.05). Key training adaptations included an increase in proteins of the malate–aspartate shuttle and citric acid cycle, reduced the abundance of glycolytic proteins, and altered the abundance of cytoskeleton proteins.The data from this study support the ability of exercise training to alter the abundance of proteins that regulate metabolism and cytoskeletal structure in patients with T2D. These findings open new avenues for future research.