Abstract:Objective To explore the immune mechanism of the Yiqi Heyingformula in treating granulomatous lobular mastitis（GLM）based on the polarization of macrophage M1/M2 phenotypes in the local immune micro environment.Methods A total of 100 GLM patients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from December 2021 to December 2022 were randomly divided into a treatment group（Yiqi Heyingformula group，n=50）and a control group（hormone therapy group，n=50）. The treatment group received basic treatment plus Yiqi Heyingformula with syndrome differentiation modifications，while the control group received basic treatment plus hormone therapy. The expression levels of TNF -α（tumor necrosis factor -α），F4/80（macrophage -specific marker），CD11c（M1 marker），and CD206（M2 marker）in local lesioned tissues were observed before and after treatment by immuno fluorescence double staining. Clinical symptoms and signs，treatment efficacy，incidence of adverse reactions，and recurrence rates were recorded. The immune mechanism of Yiqi Heyingformula in treating GLM was investigated.Results （1）After treatment，both groups showed reductions in mass size，pain severity scores，and symptom scores（P<0.05）. The treatment group exhibited superior clinical efficacy and a lower recurrence rate （10.42% vs 27.65%）compared to the control group（P<0.05）.（2）Before treatment，both groups showed increased macrophage and TNF -α positive cells，predominantly M1 phenotype，with an imbalanced M1/M2 ratio，promoting inflammation. After treatment ，both groups exhibited reduced macrophage and TNF- α positive cells. However ，the treatment group displayed a predominance of M2 macrophages，resolution of inflammation，and restoration of the M1/M2 ratio，whereas the control group remained M1-dominant with persistent M1/M2 imbalance. Conclusion The Yiqi Heyingformula can regulate macrophage M1/M2 phenotype polarization，improve the local immune micro environment，and exert anti -inflammatory effects.