Abstract: Objective To investigate the expressions of glial fibrillary acidic protein(GFAP)and acidic calcium-binding protein(S100β)in hippocampus of rat with stimulation of chronic unpredictable mild stress.Methods Thirty adult male Wister rats were selected for the model construction of chronic unpredictable mild stress and divided into two groups randomly.The depression group was treated with eight weeks of random stimulus.During the course,the influence of stress on learning and memory were observed by the rat step down test and the expression of S100β,GFAP protein in hippocampus were detected by immunohistochemistry.Results The GFAP and S100βimmunoreactions positive cell number in depression group were significantly increased compared with that of the control group.The reaction time was significantly longer than that of the control,the pre-reaction time was shorten obviously through the rat step down test,and the error frequence was significantly increased after 4 weeks stress.Conclusion Chronic unpredictable mild stress can affect the ability of learning and memory in rats.It can also induce depression and increase the expression of GFAP and S100β.