Abstract： Objective To observe the therapeutic efficacy of hyperbaric oxygen (HBO) for focal cerebral infraction influenced by the treatment time after permanent middle cerebral artery occlusion (MCAO) in rabbits. Methods Seventy-five male rabbits were randomly divided into simple MCAO group (n=25), MCAO+HBO group (100% O2, 250 kPa, 1 h/d, from 1 d after MCAO, n=25) and MCAO+DHBO group (100% O2, 250 kPa, 1 h/d, from 7 d after MCAO, n=25). Behaviors and volumes of infarction were observed, and microdialysis was applied to monitor the concentrations of glucose, lactate, pymvate and glutamate around the infarct foci at 1, 3, 10 and 30 d after permanent MCAO. Results Behaviors'score was lower in MCAO+HBO group than the others (P<0.05). The infarct volume from day 3 to day 30 was significantly smaller in MCAO+HBO group than in the other 2 groups (P<0.05). The lactate and pyruvate ratio was increased after MCAO in three groups, but they were lower in the MCAO+HBO group than in the others at day 1 and day 3 (P<0.05). The glutamate concentration was increased after MCAO, peaked at 3 d, but at day 1 and day 3 the glutamate concentration was lower in the MCAO+HBO group (P<0.05). Conclusions HBO treatment could protect the brain from infarction through improving the energy metabolism and decreasing the excitatory amino acids disorders around the infarct foci after MCAO in rabbits. In order to improve the therapeutic efficacy of HBO, it should be performed as possible.