Objective:To investigate the protective effect of reduced glutathione (GSH) on the hippocampal neuron of rats with severe acute pancreatitis (SAP). Methods:Seventy-two SD rats were equally assigned into 3 groups:the normal saline (NS) group,the SAP group and the GSH group. Each group included 3 subgroups:the 3,6 and 12 h groups. SAP models were established by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Rats in the NS group were injected with normal saline instead of sodium taurocholate. Rats in the GSH group were peritoneally injected with GSH at the dosage of 25 mg/100 g body weight. Nissle stain was performed to evaluate the severity of brain injury. Hippocampal neuronal apoptosis was detected by TUNEL,and NF-κB p65 expression was detected by immunohistochemistry. Results:Pathological scores of pancreatic injury were significantly lower in the groups of GSH(3 h) and GSH(6 h) than those in the groups of SAP(3 h) and SAP(6 h) (P < 0.05). Hippocampal neuronal apoptosis indexes were significantly decreased (P < 0.05). The expression of NF-κB p65 was depressed mainly in the GSH(6 h)group. Conclusion:The hippocampal neuronal apoptosis in SAP rats with brain injury is reduced by GSH through an inhibition of NF-κB p65 expression in the hippocampus.