BACKGROUND: Abdominal postoperative patients are susceptible to postoperative depression resulting from pain and stress, which can hinder their rehabilitation. Acupuncture has shown potential to relieve this condition. AIM: To analyze the mechanism by which acupuncture relieves postoperative depression in patients post-abdominal surgery. METHODS: Abdominal postoperative patients with depression between January 2015 and December 2023 at the First Affiliated Hospital of Heilongjiang University of Chinese Medicine were enrolled. Patients were divided into two groups using the random throwing method: Observation (250 cases, fluoxetine hydrochloride + acupuncture treatment) and control (250 cases, fluoxetine hydrochloride treatment). Changes in negative emotions Hamilton Depression Scale 24, serum inflammatory factors [tumor necrosis factor α, interleukin (IL)-1β, IL-6], miR-155 expression levels, and BDNF levels were assessed. RESULTS: Significant improvements were observed in the observation group compared to the control group in all assessed parameters after six weeks ( CONCLUSION: Acupuncture complies with the principle of traditional Chinese medicine syndrome differentiation and ensures the pertinence and effectiveness of treatment. In addition, it not only actively improves depressive symptoms but also effectively regulates the serum level of inflammatory factors.