For studying the role of CRF in the process of depression, chronic intra-cerebral ventricular administration of CRF in normal rats for 21 days were performed and compared with the depression model of chronic unpredictable miled stress (CUMS) in rats. The Open-field Test and Morris water Maze were employed to test the ability of locomotion and learning and memory. HPLC-UV, RT-PCR were employed to analyze the level of blood serum cortisol and the expression of CRF as well as its receptors (R1 and R2) of CUMS models. After chronic stress, the locomotion activity and spatial learning and memory ability decreased obviously, while the level of serum cortisol increased evidently, and the CRF and its receptor-1 mRNA levels were higher compared with those in normal rats. The rats with chronic administration of CRF also consistently decreased the weight gain, locomotion activity and the ability of spatial learning and memory as the CUMS model. This work demonstrates that CRF plays a very important role in the depression genesis and development, sustained elevation of CRF induced by stress may be the chief factor for depression.