The purpose of this study was to determine effects and mechanisms of vagal nerve stimulation (VNS) and additive effects of electroacupuncture (EA) on colonic inflammation in a rodent model of IBD. Chronic inflammation in rats was induced by intrarectal TNBS (2,4,6-Trinitrobenzenesulfonic acid). The rats were then treated with sham-ES (electrical stimulation), VNS or VNS+EA for 3 weeks. Inflammatory responses were assessed by disease activity index (DAI), macroscopic scores and histological scores of colonic tissues, and plasma levels of TNF-α, IL-1β and IL-6, myeloperoxidase (MPO) activity of colonic tissues. The autonomic function was assessed by the spectral analysis of the heart rate variability (HRV) derived from the electrocardiogram. It was found: 1) The area under curve (AUC) of DAI was substantially decreased with VNS+EA and VNS, and VNS+EA was more effective than VNS (P<0.001); 2) The macroscopic score was 6.43±0.61 in the sham-ES group and reduced to 1.86±0.26 with VNS (P<0.001) and 1.29±0.18 with VNS+EA (P<0.001). The histological score was 4.05±0.58 in the sham-ES group and reduced to 1.93±0.37 with VNS (P<0.001) and 1.36±0.20 with VNS+EA (P<0.001); 4) the plasma levels of TNF-α, IL-1β, IL-6 and MPO were all significantly decreased with VNS and VNS+EA, compared to the sham-ES group; 5) Autonomically, both VNS+EA and VNS substantially increased vagal activity and decreased sympathetic activity compared to sham-EA group (P<0.001, P<0.001, respectively). In conclusions, chronic VNS improves inflammation in TNBS-treated rats by inhibiting pro-inflammatory cytokines via the autonomic mechanism. Addition of noninvasive EA to VNS may enhance the anti-inflammatory effect of VNS.