This study was designed to investigate mast cell activation and related TLR4-NF-kappa B/TNF-alpha pathway variation in 3 and 7 days' rats intestinal I/R injury, and TXL's intervention effect. Rat intestine I/R injury was carried out using superior mesenteric artery occlusion model with 30 min ischemia followed 3 or 7 days' reperfusion. Rats were administered TXL ultrafine power of 0.4, 0.8 and 1.6g/kg/d respectively for 3 or 7 days after modeling. Mast cell activation was determined by immunofluorescent double staining TLR4, ANGPTL4 and microRNA126 were determined by RT-PCR. PECAM-1, NF-kappa B p65, TNF-alpha and VE-Cadherin were determined by immunohistochemical staining Intestine I/R induced massively mast cell activation and overexpressed TLR4, NF-kappa B, TNF-alpha, PECAM-1, miR126 in 3 and 7 days. VE-cadherin and ANGPTL4 expression was reduced. TXL treatment attenuated mast cell activation and inhibited TLR4, NF-kappa B, TNF-alpha, PECAM-1 over-expression in 3 and 7 days, protected VE-cadherin and ANGPTL4 protein Inflammation boomed in rats' intestine I/R injury for 3 and 7 days, characterized by mast cell and related TLR4-NF-kappa B/TNF-alpha pathway activation, accompanied with endothelial barrier dysfunction and enhanced vascular permeability. TXL treatment attenuated inflammation, protected endothelial barrier function. TXL treat intestine I/R injury, according with "Treat different diseases with the same method" in TCM theory.