〔Abstract〕 Objective To investigate the effects ofArmillariellatabescens polysaccharides(ATPS) on cell activity, occludin and ZO-1 in IEC-6 intestinal epithelial cells induced by lipopolysaccharide(LPS), and to reveal the protective mechanism ofArmillariellatabescens polysaccharides on intestinal mucosal barrier injury. Methods IEC-6 intestinal epithelial cell injury model induced by LPS was established. The injured cells were randomly divided into control group, LPS group, LPS+ATPS group and LPS+matrine group. The cell viability was observed by microscope and MTT; the cell apoptosis was detected by immunofluorescence and flow cytometry; the expression of ZO-1 and occludin was detected by Western blot. Meanwhile, Western blot was used to detect the expression of p-PERK,p-eIF2α,GRP78,CHOP and Arrb1 proteins. Results With the increase of ATPS concentration, the cell activity in the LPS+ATPS group increased, and the apoptosis rate decreased by immunofluorescence and flow cytometry compared with control and LPS group. The expression levels of occludin and ZO-1 protein were significantly higher in LPS+ATPS group than those in LPS group. The levels of p-PERK, p-eIF2α, GRP78, chop and arrb1 protein in LPS+ATPS group decreased compared with LPS group. Conclusion Armillariellapolysaccharide can protect intestinal epithelial cells from LPS mediated inflammatory injury by inhibiting the damage of occludin and ZO-1 proteins. The mechanism may be related to endoplasmic reticulum stress protein which mediates apoptosis and Arrb1(an important molecule) regulating intestinal mucosal injury.