To investigate the neural circuit of depressive symptoms derived from glucocorticoid (GC) receptor in dorsal raphe nucleus. Methods: Firstly,build the mice stress model was established, and the experiment has been divided into four groups: control group , Stresssd group, Mifepristone-treated group and Vehicle group, then injected GC receptor antagonists to test the change of inflammatory cytokines which associated with depression. The single-stimulate method was used to form the stress-state and the Behavioral test methods were used to assess the anxiety levels. Immunofluorescence was utilized to detect the GC receptors, microglial activation. Results: (1) Compared with the control group, the immunofluorescence result showed that the number of GC receptors in dorsal raphe nucleus has been increased after stress stimulate. (2) After intraperitoneal injected the GC receptor antagonists (Mifepristone; RU486) , the amount of GC receptors , activated microglial cells had all been decreased in the dorsal raphe nucleus of the mice, and the depression-like behaviors were also attenuated. CONCLUSION: The above results indicated that the Mifepristone in the regulation of microglial cell activation in dorsal raphe nucleus and eventually reduce depression-like behavior.