Objectives: We sought to investigate and prove the effect of hyperbaric oxygen therapy (HBOT) on T helper 17 (Th17)/regulatory T (Treg) cell polarization through changes in the expression of hypoxia-inducible factor-1 alpha (HIF-1α) in rheumatoid arthritis (RA) animal model. Methods: We used antigen and collagen-induced arthritis (ACIA) as a RA animal model. Sixteen male BALB/c models of ACIA mice were divided into two groups, the non-HBOT group as the control group and the HBOT group as the treatment group. Expression of HIF-1α, Th17 anti-cluster differentiation 196 (CD196), and Treg anti-interleukine 2 receptor β-chain cells (IL-2Rβ) in tissue from the left knee joint tissue were determined histologically. Oxidative stress and systemic inflammation were assessed by levels of superoxide dismutase (SOD), interleukin 17a (IL-17a), C-reactive protein (CRP), and rheumatoid factor (RF) using the enzymelinked immune-sorbent assay. The degree of arthritis was assessed by clinical scoring of paw swelling and the diameter of paw swelling. Results: We found a significant decrease (p < 0.050) in the expression of HIF-1α, Th17 (CD196), IL-17a, RF levels, and the clinical scores and the diameter of paw swelling when comparing both groups. There was no significant decrease in the level of CRP in the treatment group compared to the control group. The expression of Treg (IL-2Rβ) increased significantly (p < 0.050) and the level of SOD increased but not significantly (p > 0.050) in the treatment group compared to the control group. Conclusions: HBOT has effects on the polarization of Th17 to Treg through a decrease in expression of HIF-1α in mice with ACIA. HBOT is recommended for use as a support therapy for RA in combination with drug therapy.