To determine the efficacy of antibiotics in the prevention of pancreatic infection and the process of aggravation after induction of acute pancreatitis, antibiotic was administrated intravenously or intraarterially, starting 6 h after acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. Flomoxef, recognized as an antibiotic able to penetrate well into pancreas tissue, was selected for the present study. Animals were divided into three groups: no antibiotic given (Group A), antibiotic given intravenously as a bolus injection of 25 mg/kg every 6 h (Group B), and antibiotic infused continuously into the celiac trunk (4 mg/kg/h) (Group C). Compared with Group A, continuous intraarterial infusion of antibiotic (Group C) significantly improved the survival rate and decreased the serum levels of phospholipase A2(PLA2) activity and endotoxin. Furthermore, it completely prevented the occurrence of pancreatic infection, not only ameliorating the severity of pancreatic necrosis but also reducing the activity levels of amidase, trypsin-like enzyme, and PLA2 in pancreas tissue. Group B showed little beneficial effect. Antibiotic concentration in peripheral blood and pancreas tissue was significantly higher in Group C than in Group B. These results suggest that continuous arterial infusion of antibiotics into the feeding artery of the pancreas is an effective modality for preventing pancreatic infection and aggravation of severe acute pancreatitis.