Objective: Depression, a common affective disorder, is one of the leading causes of the global burden of diseases.It has been thought that chronic stress could be the main factor of inducing depression.Acupuncture in traditional Chinese medicine has been found to alleviate depression.However, it remains unknown whether acupuncture could affect the inflammatory response in a chronic stress rat model of depression.Methods: In the present study, rats were randomly assigned to the control group, the chronic unpredictable stress(CUS) group and the acupuncture group(CUS+Acu).The serum contents of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), IL-4 and IL-10 were measured by ELISA.Results: We found that CUS markedly increased the serum levels of pro-inflammatory cytokines(IL-1β, IL-6, TNF-α, and IFN-γ), and decreased the serum levels of anti-inflammatory cytokines(IL-4 and IL-10).Acupuncture treatment significantly reduced the serum levels of IL-1β, IL-6 and TNF-α, while increased IL-4 level in CUS rats.However, the levels of IFN-γ and IL-10 were not significantly affected by acupuncture.Conclusion: The antidepressant effect of acupuncture might be mediated by reducing the pro-inflammatory cytokines and increasing the anti-inflammatory cytokines, and modulating the balance between pro-and anti-inflammatory cytokines.