Background: Secondary infection of the inflamed pancreas is the principal cause of death after severe acute pancreatitis (AP). Although patients are not always managed early in the course of AP in clinical practice, prophylactic antibiotics that were used in experimental studies in rats were always initiated early after induction of pancreatitis. The effectiveness of antibiotics initiated later is unknown. Aim: The aim of this study was to compare the effectiveness of ciprofloxacin and meropenem initiated early versus later in the course of acute necrotizing pancreatitis (ANP) in rats. Methods: 100 Sprague-Dawley rats were studied. ANP was induced in rats by intraductal injection of 3% taurocholate. Rats were divided randomly into five groups: group I rats received normal saline as a placebo, group II and IV rats received three times daily meropenem 60 mg/kg i.p. at 2 and 24 h, respectively and group III and V rats received twice daily ciprofloxacin 50 mg/kg i.p. at 2 and 24 h, respectively, after induction. At 96 h, all rats were killed for quantitative bacteriologic study. A point-scoring system of histological features was used to evaluate the severity of pancreatitis. Results: Meropenem and ciprofloxacin initiated 2 h after induction of pancreatitis significantly reduced the prevalence of pancreatic infection (p < 0.001 and p < 0.04, respectively) as compared to controls. Neither of the antibiotics initiated later during the course of AP caused a significant decrease in pancreatic infection in rats (p > 0.05). Although the rats treated early infected less frequently than the rats treated later, the comparison reached statistical significance only in the meropenem group (p < 0.02). Conclusion: Early antibiotic treatment reduces pancreatic infection more efficiently than late antibiotic treatment in ANP in rats. Copyright (C) 2003 S. Karger AG, Basel and IAP.