OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST25) on colonic inflammatory response in mice with ulcerative colitis (UC), so as to explore its underlying mechanisms in anti-inflammatory. METHODS: In the first part of this study, 36 male C57BL/6J mice were randomly divided into normal, model, and EA groups (12 mice/group) according to their body weight. The UC mouse model was established by 3% dextran sulfate sodium (DSS) solution by free drinking for 7 consecutive days. EA (2 mA, 10 Hz) was applied to ST25 for 30 min, once daily on the 1(st), 3(rd), 5(th) and 7(th) day. The body weight and colon length of mice were measured. HE staining was used to observe the pathological changes of colon tissue. The contents of interleukin (IL) -1, IL-6, tumor necrosis factor-alpha (TNF-alpha) and chemokine ligand 1 (CXCL-1) in colon tissue were observed by MSD multiplex. In the second part of this study, 9 mice were assigned to the normal, model and EA groups (3 mice/group). The UC model was established by free drinking of 3% DSS solution for 5 consecutive days. EA (2 mA, 10 Hz) was applied to ST25 for 20 min on the 5(th) day. Immunofluorescence staining was used to detect the co-expression of ChAT+c-Fos in the dorsal vagal nucleus ( DMV ), T(13)-L(1) segment of spinal cord and S(2)-S(4) segment of sacral spinal cord. RESULTS: (1) Compared with the normal group, colon length and body weight were decreased (P<0.001) in mice of the model group, while the pro-inflammatory factors IL-1, IL-6, TNF-alpha and CXCL1 were significantly increased (P<0.01, P<0.001). Compared with the model group, colon length and body weight were increased (P<0.001) in mice of the EA group, while the contents of pro-inflammatory factors IL-6 and CXCL1 were decreased (P<0.01, P<0.05). H.E. staining showed severe damage of the colonic tissue with infiltration of a large number of inflammatory cells in the model group, which was milder in EA group. (2) Compared with the normal group, there was no significant difference in the expression levels of c-Fos in ChAT-positive neurons in the DMV region, and the lateral horns of T(13)-L(1) and S(2)-S(4) spinal cord in the model group. After the EA intervention, the expression levels of c-Fos in ChAT-positive neurons in the T(13)-L(1) and S(2)-S(4) lateral horns of the spinal cord were significantly increased compared with the model group (P<0.001, P<0.05). CONCLUSIONS: EA at ST25 can effectively alleviate the inflammatory lesions and down-regulate the levels of pro-inflammatory cytokines in UC mice, which may be related to the activation of segmental sympathetic and/or sacral parasympathetic nervous innervating the colon, instead of the activation of descending vagal nerves.