OBJECTIVE: Autologous blood acupoint injection has practiced for treatment of various diseases, but its therapeutic mechanism remains unknown. This study aimed to explore the histological changes in the acupoint area after blood injection. METHODS: Blood samples (0.1 mL) collected from donator mice was injected in the recipient mice at the acupoint of left Zusanli (ST- 36). At 0, 6, 12, 24, 48, 72 and 96 h after the injection (3 mice at each time point), peripheral blood and muscular tissue were collected from the injection site for blood cell classification and histological study with HE staining. RESULTS: White blood cells and lymphocytes tended to increase but platelets tended to decrease at the acupoint after blood injection, but these changes were not statistically significant. Within 24 h after blood injection, acute inflammation occurred at the acupoint, and the injected blood components were infiltrated by neutrophils; a small number of monocytes were observed at the injection site, where red blood cells gradually disappeared. From 24 to 96 h, the injected area showed chronic inflammation with infiltration by mononuclear cells, macrophages, and lymphocytes, and the number of fibroblasts increased and neutrophils decreased gradually over time; the local muscle fibers were destroyed, and proliferation of fibrous tissue could be seen. CONCLUSIONS Blood injection at the acupoints can mimic the process of hematoma absorption in the muscular tissue, and local inflammation is initiated to engulf and clear the blood components, which may be the basis for the therapeutic effects induced by acupoint stimulation.