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The aim of the study was to observe the role of nucleotide-binding and oligomerization domain (NOD)-like receptors (NLR) in intestinal injury of severe acute pancreatitis (SAP) in rats.Severe acute pancreatitis was induced by retrograde infusion of sodium taurocholate into the biliopancreatic duct. Rats were divided into the following 6 groups: sham operation, SAP treated with saline, and SAP treated with interleukin 1β (IL-1β)-converting enzyme inhibitor, killed at 6 or 12 hours after operation. Serum IL-18 and IL-1β concentrations were measured. mRNA expression and protein levels of NOD1, NOD2, and NLRP3 in the intestine were measured.Severe acute pancreatitis resulted in significantly higher serum IL-18 and IL-1β concentration, higher mRNA expression, and protein levels of NOD1, NOD2, and NLRP3 in intestine in SAP treated with saline groups compared with sham operation groups. This effect was attenuated by administration of IL-1β–converting enzyme inhibitor.The NLRs, including NOD1, NOD2, and NLRP3, were involved in the intestinal injury in SAP through a caspase-1 pathway.