OBJECTIVE Chronic stress is one of the important factors in the development of many mental and neurological diseases, and cause damage to the central nervous system, affect animal emotions and damage the immune function of the body. The purpose of this study was to investigate the effects of LW-AFC which extracting from traditional Chinese medicine prescription Liuwei Dihuang decoctionon the anxiety-like behaviorand immune dysfunction abnormalities caused by chronic stress, and whether immune intervention affect the action of LW-AFC. METHODS Male BALB/c mice were subcutaneously injected with corticosterone(25 mg·kg;) for 28 d to establish a chronic stress model. Cyclophosphamide(Cy, 80 mg·kg;) was injected continuously for the initial three days, followed by once a week, LW-AFC(1.6 g·kg;)was given continuously for 28 d. Then investigate the emotion changes by open field and elevated plus maze tests, and detected the lymphocyte proliferation, lymphocyte subsets in peripheral blood, microglia and astrocyte expression, and inflammatory cytokines in peripheral blood and brain tissue. RESULTS The mice showed obvious depressive-like behaviorafter 28 d of continuous corticosterone injection. LW-AFC could significantly improve the anxietybehavior induced by corticosterone injection, but LW-AFC could not improve the anxietybehavior of mice by Cy intervention. The expression of glial cells in hippocampus of corticosterone-induced mice showed an upward trend, and the activation of microglia and astrocytes have significantly increase in corticosterone and Cy injected mice. LW-AFC significantly decreased the activation of microglia and astrocytes in corticosterone-induced mice with Cy intervention. This suggested that LW-AFC can reduce the damage of stress on the immune function of central nervous system under immunosuppressive state. Furthermore, LW-AFC could significantly up-regulate the proliferation of splenic lymphocyte stimulated by LPS and Con A, up-regulate the proportion of CD3+CD8+cells, reduce the proportion of CD4+/CD8+cells, decrease the secretion of inflammatory factors IL-6 and MCP-1 in plasma, and increase the level of anti-inflammatory factor IL;0 in plasma of mice induced by chronic corticosteroneinjection. While LW-AFC could promote the inflammatory factors TNF-αand IL-6 in plasma, inhibit the secretion of anti-inflammatory factor IL;0 and inflammatory cytokine MCP-1 in hippocampus of corticosterone-induced mice with Cy intervention. CONCLUSION LW-AFC can improve anxiety-likebehavior induced by chronic stress, the Cy intervention affects the alleviation of anxiety-like behavior by LW-AFC as well as the regulation of immune function. The regulation of immune function might be the main way for LW-AFC to improve the function of central nervous system.