The purpose of this study was to investigate the effects of hyperbaric oxygen therapy (HBOT) on inflammation, the oxidative/antioxidant balance, and muscle damage after acute exercise in normobaric, normoxic (NN) and hypobaric, hypoxic (HH) environments. Eighteen healthy males were selected and randomly assigned to three groups: exercise in NN conditions (NN group, n = 6), HBOT treatment after exercise in NN conditions (HNN group, n = 6), and HBOT treatment after exercise in HH conditions (HHH group, n = 6). All subjects performed treadmill running for 60 min at 75–80% maximum heart rate (HRmax) exercise intensity under each condition. The HBOT treatments consisted of breathing 100% oxygen at 2.5 atmosphere absolute (ATA) for 60 min. Blood samples were collected before exercise (BE), after exercise (AE), and after HBOT (AH) to examine inflammation (fibrinogen, interleukin-6 [IL-6], and tumor necrosis factor-α (TNF-α)), the oxidative/antioxidant balance (derivatives of reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP)), and muscle damage (creatine kinase (CK) and lactate dehydrogenase (LDH)). Plasma fibrinogen, serum IL-6, CK, and LDH levels were significantly increased AE compared to BE in all groups (p < 0.05). Plasma fibrinogen levels were significantly decreased AH compared to AE in all groups (p < 0.05), and the HNN group had a significantly lower AH compared to BE (p < 0.05). Serum IL-6 levels were significantly decreased AH compared to AE in the HNN and HHH groups (p < 0.05). Serum CK levels were significantly decreased AH compared to AE in the HHH group (p < 0.05). Serum LDH levels were significantly decreased AH compared to AE in the HNN and HHH groups (p < 0.05), and the NN and HNN groups had significantly higher AH serum LDH levels compared to BE (p < 0.05). These results suggest that acute exercise in both the NN and HH environments could induce temporary inflammatory responses and muscle damage, whereas HBOT treatment may be effective in alleviating exercise-induced inflammatory responses and muscle damage.