Abstract: OBJECTIVE To study the changes of macrophage-related cytokines in the development of depression， and to explore the immunological mechanism of acupuncture on treating depression.METHODS Chronic unpredictable mild stress (CUMS) was employed to induce depression in mice and open-field test and sucrose preference test were operated during the progress of depression. Simultaneously， the peritoneal macrophages were isolated from mice and were cultured under the stimulation with LPS， ELISA method were used to measure the contents of TNF-α， IL-1β and IL-6 in the supernatant of peritoneal macrophages. Depression mice were given treatment of acupuncture， and the effect of behavior change was observed and the content of macrophage cytokine production was measured respectively.RESULTS 21 days after making model， the model of chronic unpredictable mild depression was generally developing， the secretion ability of IL-1β and IL-6 in the middle or late stage increased significantly， while the ability of TNF-α did increase but not that obvious. After treatment of acupuncture， behavior indicator was improved and meanwhile the ability of secreting TNF-α， IL-1β， IL-6 decreased significantly. CONCLUSION The ability of modeling mice secreting inflammatory cytokines by peritoneal macrophages increased in the formation of CUMS depression， which acupuncture can significantly regulate might be one of the mechanisms in improving behavior change.