Aim: To investigate if exercise can reverse starvation-induced insulin resistance and to elucidate the mechanism. Methods: Nine subjects underwent 87 h of starvation with (EX) or without (NE) one exercise session at the end. Before and after starvation (3 h post-exercise) subjects underwent an intravenous glucose tolerance test and muscle biopsy. Results: Insulin sensitivity decreased after starvation (NE) but increased after exercise (EX). Glycogen stores were reduced and plasma FA and β-Hydroxybutyrate increased in both conditions. Mitochondrial respiration with FA substrate increased in EX but was unchanged in NE. RCR and mitochondrial ROS production decreased in both conditions. Phosphorylation of Acetyl-CoA carboxylase (ACC) and Akt substrate of 160 kDA (AS160) proteins increased in EX. Conclusion: Exercise improves starvation induced insulin resistance, probably by increased mitochondrial FA oxidation, reduced glycogen stores and alterations in signaling proteins involved in glucose uptake and FA metabolism.