To observe the therapeutic effect and mechanism of Ningxin Jieyu acupuncture on post-stroke depression(PSD).Methods:Seventy-five PSD patients admitted to The First Hospital of Hunan University of Chinese Medicine from January 2022 to December 2023 were taken as research subjects and randomly divided into an observation group，a control group，and a sham group，with 25 cases in each group.Changes in the following aspects were observed after 4 weeks and 8 weeks of treatment：depression degree，neurological function，hypersensitive C-reactive protein(hs-CRP)，interleukin-6(IL-6)，and homocysteine(Hcy).Results:Compared with the condition before treatment，the depression degree，as well as hs-CRP，IL-6，and Hcy levels of the 3 groups of subjects were improved after 4 weeks and 8 weeks of treatment(P<0.05).Compared with 4 weeks of treatment，all indices were further improved after 8 weeks of treatment(P<0.05).Depression improvement comparison：After 4 weeks of treatment，the observation group was better than the control group and the sham group(P<0.05)，and the control group was better than the sham group(P<0.05).After 8 weeks of treatment，there was no statistically significant difference in scores between the observation group and the control group(P>0.05)，while the scores of the observation group and the control group were better than the sham group(P<0.05).Neurological function improvement comparison：After 4 weeks of treatment，the observation group was better than the control group and the sham group(P<0.05).After 8 weeks of treatment，the observation group was better than the control group and the sham group(P<0.05)，while the control group was better than the sham group(P<0.05).Comparison of improvement in hs-CRP，IL-6，and Hcy levels：After 8 weeks of treatment，there was no statistically significant difference in hs-CRP，IL-6，and Hcy levels between the observation group and the control group(P>0.05).The improvement of hs CRP，IL-6，and Hcy levels in the observation group and control group was more significant than that in the sham group(P<0.05).Conclusion:Ningxin Jieyu acupuncture can effectively improve depressive symptoms and neurological function in PSD patients，while effectively reducing serum hs-CRP，IL-6，and Hcy levels.