To gain a global view of the genomic response of neurons to normobaric and hyperbaric hyperoxic stress, we performed a microarray analysis of gene expression after exposure to varying levels of partial oxygen pressures. Rat neurons were exposed to normobaric hyperoxia, hyperbaric (2, 4, and 6 atmosphere absolute) air or hyperbaric O2. We identified 183 genes significantly altered (increased or decreased ≥1.5-fold) in response to pressure and/or oxidative stress. Among them, 17 genes changed in response to all exposure conditions. More genes were altered in response to hyperbaric air than hyperbaric O2. The altered genes included factors associated with stress responses, transport/neurotransmission, signal transduction, and transcription factors. The results may serve as guidance for selection of biomarkers of hyperoxia and hyperbaric O2 response and provide a starting point for further studies to investigate the global molecular mechanisms underlying hyperbaric oxidative stress.