Background <p>Hyperbaric oxygen (HBO) treatment can attenuate the inflammatory response after spinal cord injury (SCI), but the specific molecular mechanisms are unclear. γδT cells have emerged as key immune regulatory cells. This study aims to analyze the mechanism of HBO treatment reducing SCI mainly from the perspective of γδT cells.</p> Methods <p>Contusion SCI models were established in WT, TCRδ^−/−, and IL-17^−/− mice, and HBO treatment was performed. Hindlimb locomotor function, ChAT-positive motor neuron numbers, γδT cell proportion, and inflammatory cytokines level of different experimental groups were compared after SCI. Furthermore, we measured the protein and gene expression of STAT3 and RORγt in both WT mice and STAT3 overexpression mice following HBO treatment.</p> Results <p>Our results showed γδT cells, especially IL-17 + γδT cells, were involved in SCI. HBO treatment improved locomotor recovery, reduced the proportion of γδT and IL-17 + γδT cells, and decreased inflammatory cytokines in WT mice after SCI. However, HBO treatment did not affect locomotor recovery or inflammatory cytokines level in TCRδ^−/− or IL-17^−/− mice after SCI. In addition, HBO treatment significantly inhibited the expression of STAT3 and RORγt in WT mice after SCI. Over-expression of STAT3 weakened the inhibitory effect of HBO on IL-17 + γδT cells and inflammatory cytokines after SCI.</p> Conclusions <p>These findings indicated that IL-17 + γδT cells may play a key role in HBO treatment alleviating the inflammatory response after SCI. HBO treatment may regulate IL-17 + γδT cells by modulating the pathway of STAT3/RORγt. This study provides the theoretical basis and potential therapeutic target for HBO treatment in SCI.</p>