Background context Spinal cord injury (SCI) is a serious health issue that may result in high health care costs, with additional social and psychological burdens.Hyperbaric oxygen (HBO) treatment has been found to be beneficial for neurological recovery; however, the underlying mechanisms are yet to be characterized.Purpose The aim of this study was to investigate the mechanisms of HBO treatment in SCI by measuring the expression levels of vascular endothelial growth factor (VEGF) and Connexin43 (CX43) in the injured spinal cord tissue.Study design: An experiment animal study of rats undergoing SCI and HBO treatment.Methods The spinal cord injury model was established in rats, which were randomly divided into the following four groups: (1) the sham-operated group (SH), (2) the sham-operated and hyperbaric ox ygen treatment group (SH+HBO), (3) the spinal cord injury group (SCI), and (4) the spinal cord injury and hyperbaric oxygen trearment group (SCI+ HBO).For groups of SH+HBO and SCI+ HBO, the animals received 1 hour of HBO at 2.0 ATA ir 100% O2 twice per day for 3 days and then daily for the following days consecutively after surgery.After operation, neur)logical assessments were performed, the spinal cord tissue samples were harvested for histopathological evaluation, Western blot and real-time polymerase chain reaction analysis.Results The Basso-Bettie-Bresnahan scores were signif icantly improved in the SCI+ HBO group compared with the SCI group on the postoperative 7th and 14th days.The histology scores were significantly decreased by HBO treatment compared with that in the SCI group on the postoperative 3rd, 7th, and 14th days.Western blot analysis and real-time polymerase chain reaction revealed that the expression level of vascular endothelial growth factor (VEGF) in the SCI+ HBO group was significantly increased compared with the SCI group.The protein exp ression level of CX43 and its mRNA level in the SCI+ HBO group were significantly decreased on the postoperative 3rd and 7th days, whereas its expression was significantly increased by HBO treatment on the postoperative 14th day compared with the SCI group.Conclusions HBO treatment improved neurological recovery when applied after SCI.The expression lev el changes of VEGF and CX43 may contribute to the further understanding on the molecular mechanisms of HBO treatment on SCI.