Electroacupuncture (EA) relieves visceral hypersensitivity (VH) with underlying inflammatory bowel diseases. However, the mechanism by which EA treats ileitis-induced VH is not clearly known. To assess the effects of EA on ileitis-induced VH and confirm whether EA attenuates VH through spinal PAR-2 activation and CGRP release, goats received an injection of 2,4,6-trinitro-benzenesulfonic-acid (TNBS) solution into the ileal wall. TNBS-injected goats were allocated into VH, Sham acupuncture (Sham-A) and EA groups, while goats treated with saline instead of TNBS solution were used as the control. Goats in EA group received EA at bilateral Hou-San-Li acupoints for 0.5 h at 7 days and thereafter repeated every 3 days for 6 times. Goats in the Sham-A group were inserted with needles for 0.5 h at the aforementioned acupoints without any hand manipulation and electric stimulation. Visceromotor responses to colorectal distension, an indicator of VH, were recorded by electromyography. The terminal ileum and thoracic spinal cord (T 11) were sampled for evaluating ileitis at days 7 and 22, and distribution and expression-levels of PAR-2, CGRP and c-Fos on day 22. TNBStreated-goats exhibited apparent transmural-ileitis on day 7, microscopically low-grade ileitis on day 22 and VH at days 7-22. Goats of Sham-A, VH or EA group showed higher (P < 0.01) VH at days 7-22 than the Control-goats. EA-treated goats exhibited lower (P < 0.01) VH as compared with Sham-A or VH group. Immunoreactive-cells and expression-levels of spinal PAR-2, CGRP and c-Fos in the EA group were greater (P < 0.01) than those in the Control group, but less (P < 0.01) than those in Sham-A and VH groups on day 22. Downregulation of spinal PAR-2 and CGRP levels by EA attenuates the ileitis and resultant VH. Inflammatory bowel diseases (IBDs) are chronic, immune-mediated and remittent-relapsing gastrointestinal inflammation. Crohn's disease (CD) and ulcerative colitis (UC) are the predominant clinical types of IBDs and their resultant symptoms include diarrhea, nausea, weight loss, abdominal pain and visceral hypersensitivity (VH) 1,2. There are two-thirds of IBD patients suffering from VH during their acute flares and remission 3,4. The persistent nature of VH impairs the patient's quality of life and consumes huge medical resources throughout the world. The environmental stress, inflammation and traumatic injuries trigger the development of VH. However, its underlying mechanism is not completely understood. A G-protein coupled receptor, PAR-2, is activated due to proteolytic cleavage of trypsin, tryptase and cathepsin-S 5-7. Over the years, studies have reported that the PAR-2 activation on resident mast cells, neutrophils or macrophages initiates for the release of inflammatory mediators, i.e., cytokines, chemokines and prostaglandins, which triggers the production of neurogenic mediators, i.e., substance-P (SP) and calcitonin gene-related peptide (CGRP) from the enteric neurons as well as afferent nerves to elicit eventually the VH 8-10. Cenac et al. 11 infu...