Severe burns initiate an inflammatory cascade within the gut, which leads to intestinal mucosal injury.Although the Na-/H-exchanger 1 (NHE1) is recognized as a pivotal player in several inflammatory processes, its role in burn-induced intestinal injury is relatively unknown.We hypothesized that NHE1 might be involved in the increased intestinal permeability and barrier breakdown after severe burns.Thus, we here investigate whether the inhibition of NHE1 has a protective effect on burn-induced intestinal injury.Mice were subjected to a 30% total body surface area (TBSA) full thickness steam burn.Cariporide was used to assess the function of NHE1 in mice with burn-induced intestinal injury by fluorescence spectrophotometer, Western blotting and ELISA assay.We found that severe burn increased intestinal permeability, associated with the up-regulation of NHE1 and raised inflammatory cytokine levels.Mice treated with the NHE1 inhibitor cariporide had significantly attenuated burn-induced intestinal permeability and a reduced inflammatory response.NHE1 inhibition also reduced NF-κ B activation and attenuated p38MAPK phosphorylation.Our study suggests that NHE1 plays an important role in burn-induced intestinal permeability through the regulation of the inflammatory response.The inhibition of NHE1 may be adopted as a potential therapeutic strategy for attenuating the intestinal barrier breakdown.