Objective To determine whether regional arterial infusion (RAI) of 5-Fu and imipenem could decrease infection and mortality of acute necrotic pancreatitis (ANP) or not. Methods Fifty three patients with ANP were devided into three groups, group A, 16 patients who received intravenous 5-Fu and imipenem, group B, 22 patients who received 5-Fu by RAI and imipenem intravenously, and group C, 15 patients who received both 5-Fu and imipenem by RAI. Results The incidence of infection of ANP in group C (0%) was significantly lower than that in group A (50.0%) and B (27.2%), and the mortality rates in group B (18.1%) and C (13.3%) were significantly reduced as compared with group C (43.8%). Conclusion RAI of 5-Fu and imipenem was effective in reducing ANP infection and mortality rates.