Objective To explore the effect of oridonin on the endoplasmic reticulum stress (ERS) in colonic epithelium of ulcerative colitis (UC) mice.Methods The UC mice model was established by sodium dextran sulfate (DSS),and the intervention group of oridonin and sulfasalazine was set up,the disease activity index (DAD was measured,the colonic tissue was evaluated by histopathologidscore (HPS),and RT-qPCR was used to detect the expression of inflammatory cytokines tumor factor-α (TNF-α),interleukin 6 (IL-6),cyclooxygenase 2 (COX-2),glucose-regulated protein 78 (GRP78),transcription factor EBP homologous protein (CHOP),activator transcription factor 6 (ATF6),protein kinase R like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme 1α (IRE1α).Results The expression of TNF-α,IL-6,COX-2,GRP78,ATF6,CHOP,PERK and IRE1α mRNA in the colonic epithelium of the model group were all up-regulated obviously as compared with the healthy control group(P＜0.05,P＜0.01).When compared with the model group,DAI and HPS in oridonin-treated group were significantly decreased (P＜0.05,P＜0.01),which the curative effect was similar to that of the sulfasalazine group(P＞0.05,P＜0.01).The expression of TNF-α,IL-6,COX-2,GRP78,CHOP,ATF6 and PERK mRNA levels were significantly reduced in oridonin-treated group(P＜ 0.05,P＜0.01).Conclusion Oridonin can alleviate colonic inflammation induced by DSS and its mechanism may be related to ERS of colonic epithelial tissue.