Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods: A total of 60 rats were divided into 5 groups: blank control, 10-6 mol/L dexamethasone (DEX) group, 10-9 mol/L DEX group,0.9% saline group and GR blocking group (10-2mol/L RU486). All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy (LCSM); CRH mRNA level was explored by in situ hybridization. Results: 10-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion: High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.