OBJECTIVE: To observe the action of Na + K + ATPase of the brain in neonatal rats with hyperbilirubinemia and to explore the pathogenesis of bilirubin encephalopathy. METHODS: Seventy two 7 day old SD rats were randomly assigned to the control group and the experiment group. The rats of the experiment group were subdivided into 5 groups: T 1, T 2, T 3, T 4 and T 5 groups according to the increased bilirubin injected intraperitoneally. And the hyperbilirubinemic animal model was established. The bilirubin contents in the brain and serum were measured and the action of Na + K + ATPase in the brain was assayed by measuring the inorganic phosphorous content per milligram protein of brain tissues in the rats. RESULTS: Four and 8 hours after the bilirubin injection, as the injected bilirubin was increasing, the serum total bilirubin concentration and the brain bilirubin content were increasing, and the action of Na + K + ATPase in the brain was decreasing. Except for the T 1 group, there were significant differences in all the experiment groups compared with the control group (P< 0.05 or 0.01 ). No difference was found in the serum bilirubin content between 4 and 8 hours after the bilirubin injection in all the experiment groups, while there were significant differences in the brain bilirubin content and the action of Na + K + ATPase in the brain between 4 and 8 hours after the bilirubin injection in the T 2～T 5 groups (P< 0.05 ). There was negative relation between the bilirubin content and the action of Na + K + ATPase in the brain (r= -0.86 , P< 0.01 ). No relation was noted between the serum total bilirubin concentration and brain bilirubin content. CONCLUSIONS: The bilirubin might inhibit the action of Na + K + ATPase in the brain.