Objective To study the relationship between oxygen free radical and phospholipase A2 and therapeutic effect of naltrexone (NTX) on experimental pancreatic encephalopathy (PE) induced by acute hemorrhagic necrotizing pancreatitis (AHNP) in rats. Methods A model of experimental PE in AHNP was induced by retrograde injection of 5% sodium taurocholate into the pancreatic duct. The rats were randomly divided into three groups: control group, PE group and NTX group. The plasma and cerebral levels of malondialdenhyde(MDA), scavengers superoxided ismutase(SOD), and phospholipase A2 (PLA2) were determined in both PE and NTX groups. Changes of the pancreatic and cerebral histology were examined by light and electric microscopy. Results In NTX treatment phase, the MDA and PLA2 were significantly fall, while SOD was increased in the plasma and cerebral tissue, the damage to pancreatic and cerebral tissue was emiliorated. Conclusion The experimental model of PE on rats is an ideal one for PE investigation. NTX could decrease oxygen free radicals and PLA2 activity and improve the damage to cerebral and pancreatic tissue. The lethality rate in rats of PE is significantly low after NTX treatment.