Objective To investigate the therapeutic effects of glucocorticoids(GC)on brain damage in rats with severe acute pancreatitis(SAP).Methods Thirty two rats were randomized into the normal control group(Group A),acute pancreatitis group(Group B),common carotid therapeutic group(Group C)and lateral ventricle therapeutic group(Group D).The rats in group C and D were respectively given methylprednisolone through common carotid artery and lateral ventricle. All rats were killed 24r h later to determine the weight of water content in the brain.The pancreatic and brain tissues were stained with HE.Meanwhile,the brain samples were immunohistochemically stained and the medulla sheath specially stained to determine TNF-α and IL-2.Histopathological scoring of pancreas and counting of leukocytes in the brain were conducted.Results Group A had no obvious pathologic changes.Group C and D had fewer TNF-α positive cells in the brain than Group B.IL-2 was negative in each group.Brain edema,leukocyte number and demylination of myelinated nerves in Group C and D were significantly different from those in Group B(P＜0.05).Conclusion Demylination of myelinated nerves is the characteristic change in SAP.Brain edema,leukocyte infiltration and nerve cell degeneration would happen as well.TNF-α plays an important role in the development of SAP.GC has effects on prevention and therapy of brain damage in rats with SAP.