INTRODUCTION: Prediabetes is a major risk factor for type 2 diabetes and cardiovascular diseases. While resistance exercise (RE) is recommended for individuals with prediabetes, the effects of RE on postprandial glucose metabolism in this population are poorly understood. Therefore, the purpose of this study was to elucidate how RE affects postprandial glucose kinetics, insulin sensitivity, beta cell function, and glucose oxidation during the subsequent meal in sedentary men with obesity and prediabetes. METHODS: We studied 10 sedentary men with obesity (BMI: 33 ± 3 kg/m) and prediabetes by using a randomized, cross-over study design. After an overnight fast, participants completed either a single bout of whole-body RE (7 exercises, 3 sets of 10-12 repetitions at 80% 1-repetition maximum each) or an equivalent period of rest. Participants subsequently completed a mixed meal test in conjunction with an intravenous [6,6-H2]glucose infusion to determine basal and postprandial glucose rate of appearance (Ra) and disappearance (Rd) from plasma, insulin sensitivity, and the insulinogenic index (a measure of beta cell function). Skeletal muscle biopsies were obtained 90 min post-meal to evaluate pyruvate-supported and maximal mitochondrial respiration. Whole-body carbohydrate oxidation was assessed using indirect calorimetry. RESULTS: RE significantly reduced the postprandial rise in glucose Ra and plasma glucose concentration. Postprandial insulin sensitivity was significantly greater after RE, while postprandial plasma insulin concentration was significantly reduced. RE had no effect on the insulinogenic index, postprandial pyruvate respiration, or carbohydrate oxidation.Conclusion/InterpretationA single bout of RE has beneficial effects on postprandial glucose metabolism in men with obesity and pre-diabetes by increasing postprandial insulin sensitivity, reducing the postprandial rise in glucose Ra, and reducing postprandial plasma insulin concentration.