This study was designed to (1) investigate the effects of acute hyperbaric exposure on muscle mRNA expression levels, and (2) clarify the mechanisms by which intermittent hyperbaric exposure improves endurance capacity. Experiment 1: Male mice were subjected to acute 1-h hyperbaric exposure (1.3 atmospheres absolute with 20.9% O2). The expression of peroxisome pro- liferator-activated receptor gamma coactivator 1-alpha (PGC-1a) mRNA sig- nificantly increased in the soleus (7.2-fold) and red gastrocnemius muscles (Gr, 5.1-fold) 3 h after hyperbaric exposure. Peroxisome proliferator-activated receptor alpha (PPARa) mRNA levels significantly increased in the plantaris (PL, 2.9-fold) and Gr (2.3-fold) 3 h after hyperbaric exposure. Experiment 2: Mice were subjected to exercise training with (HypTr) and without (Tr) 1-h hyperbaric exposure for 4 weeks. Increases in maximal exercise capacity were significantly greater in HypTr than in Tr. In PL, activity levels of 3-hydroxy- acyl-CoA-dehydrogenase and citrate synthase (CS) were significantly greater in HypTr than in Tr. CS and phosphofructokinase activities both markedly increased in the white gastrocnemius muscle (Gw) in HypTr only. PGC-1a expression in the nucleus was significantly greater in HypTr than in Tr in PL (4.8-fold), Gr (3.2-fold), and Gw (15-fold). Protein levels of mitochondrial transcription factor A and heat shock protein 70 significantly increased after training with hyperbaric exposure. These results suggest that exercise training with intermittent hyperbaric exposure represents a beneficial strategy for increasing endurance performance by facilitating oxidative and glycolytic capacities and the expression of proteins involved in mitochondrial biogenesis in the hindlimb muscles.