BACKGROUND: Emodin, a traditional Chinese medicine, has a therapeutic effect on severe acute pancreatitis (SAP), whereas the underlying mechanism is still unclear. Studies showed that the intestinal mucosa impairment, and subsequent release of endotoxin and proinflammatory cytokines such as IL-1β, which further leads to the dysfunction of multiple organs, is the potentially lethal mechanism of SAP. Caspase-1, an IL-1β-converting enzyme, plays an important role in this cytokine cas-cade process. Investigation of the effect of emodin on regulating the caspase-1 expression and the release proinflammatory cyto-kines will help to reveal mechanism of emodin in treating SAP. METHODS: Eighty Sprague-Dawley rats were randomly di-vided into four groups (n=20 each group): SAP, sham-operat-ed (SO), emodin-treated (EM) and caspase-1 inhibitor-treated (ICE-I) groups. SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct. Emodin and caspase-1 inhibitor were given 30 minutes before and 12 hours after SAP induction. Serum levels of IL-1β, IL-18 and endotoxin, histopathological alteration of pancreas tissues, in-testinal mucosa, and the intestinal caspase-1 mRNA and pro-tein expressions were assessed 24 hours after SAP induction. RESULTS: Rats in the SAP group had higher serum levels of IL-1β and IL-18 (P<0.05), pancreatic and gut pathological scores (P<0.05), and caspase-1 mRNA and protein expressions (P<0.05) compared with the SO group. Compared with the SAP group, rats in the EM and ICE-I groups had lower IL-1β and IL-18 levels (P<0.05), lower pancreatic and gut pathologi-cal scores (P<0.05), and decreased expression of intestine cas-pase-1 mRNA (P<0.05). Ultrastructural analysis by transmis-sion electron microscopy found that rats in the SAP group had vaguer epithelial junctions, more disappeared intercellular joints, and more damaged intracellular organelles compared with those in the SO group or the EM and ICE-I groups. CONCLUSIONS: Emodin alleviated pancreatic and intestinal mucosa injury in experimental SAP. Its mechanism may partly be mediated by the inhibition of caspase-1 and its down-stream inflammatory cytokines, including IL-1β and IL-18. Our animal data may be applicable in clinical practice.