Increasing evidences demonstrate that immune dysregulation can result in depression, and it is reported that persistent inflammatory response is related to the unresponsiveness of antidepressant treatment.This study aimed to explore the reason why some responded but some not responded to acupuncture in treating postpartum depression (PPD), and whether it related to the levels of inflammatory cytokines.Women diagnosed with PPD were recruited in to accept 8-week acupuncture. All subjects were assessed the 17-item Hamilton Depression Rating Scale (HDRS17) at baseline, week 1, week 2, week 4 and week 8 during the treatment. A panel of 9 cytokines was measured at baseline and 8 weeks.Of the 121 participants, 96 completed the 8-week assessment and 46 completed the blood sample collection. HDRS17 scores of 96 subjects showed significant statistical reduction since the first week (P = 0.002) and reached to 5.31 (P < 0.000) at the end of therapy. And we divided the 46 subjects into responders and non-responders according to the response rate of HDRS17 scores. Responders and non-responders did not differ significantly between-group in changes in the 9 cytokines. In responders, IL-6, IL-10 and IFN-γ levels were statistically lower (P = 0.006; P = 0.033; P = 0.024), while TGF-β1 was statistically higher after 8 weeks treatment (P < 0.000). In non-responders, the levels of IL-5, TNF-α and TGF-β1 were statistically higher (P = 0.018; P < 0.000; P < 0.000), while IFN-γ was statistically lower (P = 0.005).Acupuncture could alleviate depressive symptoms of patients with PPD and might through adjusting peripheral inflammatory response by up-regulating anti-inflammatory cytokines and down-regulating pro-inflammatory cytokines.© 2023 Xu et al.