This study was designed to evaluate the possible role of cytokines (IL-1 and TNF-alpha) in the pathogenesis of pancreatic injuries induced by pancreatic ischemia-reperfusion and to evaluate the protective effect of the cytokine suppressive agent, FR167653, against pancreatic injuries. Pancreatic ischemia-reperfusion was induced in rats by ligating the celiac and caudate mesenteric arteries by small metallic clips for 45 min, after this ischemia, the metal clips were removed. Four hours after removing the metal clips, the animals were used for the experiments. In this model, mild hyperamylsemia and significant increases in pancreatic water and trypsin content were observed. Significant increases in serum IL-1 and TNF-alpha were also observed, as compared with the control rats. Pancreatic subcellular redistribution of lysosomal enzyme cathepsin B from the lysosomal fraction to the zymogen fraction was also observed. However, treatment with FR167653 at a dose of 0.5 mg/kg.hr significantly prevented all these pancreatic injuries. These results indicate that cytokines such as IL-1 and TNF-alpha might be involved in the pathogenesis of pancreatic injuries induced by ischemia-reperfusion, and that a cytokine suppressive agent might be of therapeutic value for the treatment of pancreatic ischemia.