Objective To evaluate the effect of the hyperbaric oxygenation therapy on the apoptosis of the hippocampal neuron and the impairment of cognitive function of the newborn rats suffering from bilirubin encephalopathy. Methods One hundred and forty-five five-day-old SD rats of both sex were randomly divided into 3 groups,control group,bilirubin encephalopathy group and hyperbaric oxygenation treated group. Bilirubin ( 10 mg/ml) was injected into the cerebellomedullary cistern to establish experiment model,and normal sodium was injected for control. The expression of cytochrome C and Caspase-3 in the hippocampus neurons were detected by immunohistochemistry and immunofluorescence,respectively,at the time of 6 h,1,3,5 d and 7 d after intra-cisternal injection. Neuronal apoptosis was checked by TUNEL method. The cognitive function was tested by Morris experiment. Results The expressions of the cytochrome C and Caspase-3 in hyperbaric oxygenation treated group were lower than those in bilirubin encephalopathy group,but higher than control group at abovementioned time points ( P