Chelidonic acid (CA), a constituent of Chelidonium majus L., has many pharmacological effects, including mild analgesic and antimicrobial effects. However, the effects of CA on intestinal inflammation and the molecular mechanisms responsible are poorly understood. The aim of this study was to investigate the protective effects of CA against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). Mice treated with DSS displayed obvious clinic signs, such as, body weight loss and a shortening of colon length, but the administration of CA attenuated both of these signs. Additionally, CA was found to regulate levels of interleukin-6 and tumor necrosis factor-α in serum. In colonic tissues, prostaglandin E(2) (PGE(2)) production levels and cyclooxygenase-2 (COX-2) and hypoxia induced factor-1α (HIF-1α) expression levels were increased by DSS, but CA attenuated increases in COX-2 and HIF-1α levels. These results provide novel insights into the pharmacological actions of CA and its potential use for the treatment of intestinal inflammation.