Background Intestinal ischemia-reperfusion (IIR) is implicated in the pathogenesis of severe acute pancreatitis (SAP). This study investigates the impact of neurocrine somatostatin (SST) on the contraction of sphincter of Oddi (SO) during IIR. Methods Intestinal ischemia-reperfusion model in macaques was induced by occluding the superior mesenteric artery. Pancreatitis was confirmed by pancreatic histology and serum levels of amylase and lipase. SST and its receptors (SSTRs) in SO were visualized by immunohistochemistry. Effects of SST on the contraction of the isolated SO were recorded in vitro. Key Results Inflammatory scores of the pancreas and serum levels of amylase or lipase in the macaques that underwent IIR were significantly higher than those in the control group. The frequency and amplitude of phasic contraction of the circular muscle in SO was increased by SST in a concentration-dependent manner. Compared with the control group, SST innervation or SSTR2 expression in SO of macaques treated with IIR was increased 5.2 fold or 5.6 fold respectively. Prophylactic infusion of SST before IIR significantly reduced SST immunoreactive fibers in SO as compared to those in the IIR group and remarkably alleviated the pathophysiologic changes due to IIR. Conclusions & Inferences Increased SST innervation in SO during the early phase of IIR associated with the contraction of circular muscle of SO, which might be one of the promoting factors associated with the development of SAP. Prevention of IIR or intervention of SO contraction after occurrence of acute pancreatitis might be beneficial for preventing SAP. © 2010 Blackwell Publishing Ltd.