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OBJECTIVE: To find the best pressure and time of hyperbaric oxygenation (HBO) therapy by comparing different pressures and times in a rat model of neonatal hypoxic ischemic brain damage (HIBD) and to provide the mechanisms of HBO therapy for neonatal clinical application. METHODS: 7day old SD rats were randomly divided into a control(CON) group, HIBD group and HBO group. The HBO group was divided into 7 subgroups according to the different HBO pressure: 1 ATA(H 1.0)，1.25 ATA(H 1.25), 1.5 ATA(H 1.5), 1.75 ATA(H 1.75), 2 ATA(H 2.0), 2.25 ATA(H 2.25) and 2.5 ATA(H 2.5) group. After choosing the best pressure we divided the rats into two groups according to the different HBO time: 30 min group (H 30 min) and 60 min group (H 60 min). All the rats(14dayold) were killed at 7 days after HI. Body weight increasing, left/right brain weight ratio, neuropathologic examination and superoxide dismutase(SOD) and malondialdehyde(MDA) content in brain tissue were measured in each group. RESULTS: ①The weight increasing rate ［(72.91±21.27)%］ and the left/right brain weight ratio (0.6444±0.1599) decreased obviously. At the same time the content of SOD ［(203.32±57.18) NU/ml］ in brain tissue decreased and that of MDA ［(4.197±0.683) nmol/ml］ increased in HIBD group. All above data showed a more significant difference in HIBD group compared to the control group ［weight increasing rate=(104.97±17.34)%，left/right brain weight ratio=0.9857±0.0396，SOD content=(261.53±41.38) NU/ml，MDA content=(3.393±0.574) nmol/ml］(P<0.01). ②Following the increasing HBO pressure the weight increasing rate and left/right brain weight ratio gradually increased, the content of SOD in brain tissue increased and that of MDA decreased, and to the best in H 2.0 group ［left/right brain weight ratio=0.8583±0.1544，SOD content=(259.20±45.22) NU/ml，MDA content=(3.462±0.498) nmol/ml, compared to HIBD group, P<0.01 or <0.05］. ③The weight increasing rate, left/right brain weight ratio, the content of SOD and MDA were higher in H 60min group than in H 30min group, but there was no significant difference between the two groups (P>0.05). CONCLUSIONS: HBO of 2.0 ATA pressure and 30～60 min steady time may have the best effect, and reasonable HBO treatment can increase SOD content and decrease MDA content in brain tissue in HIBD neonatal rats.