Objective: To study the effect of the Lactobacillus plantarum (LP) enteral feeding on the gut permeability and sepsis in the patients with acute pancreatitis. Subjects: Seventy-six subjects who stayed over 1 week in the hospital completed the study. Subjects were not treated with any lactobacillus supplement before the intervention. Methods: Seventy-six patients with acute pancreatitis were randomly divided into two groups, parenteral nutrition (PN) group (n ¼ 38) and ecoimmunonutrition (EIN) group supplied by LP enteral feeding (n ¼ 36). The acute physiology and chronic health evaluation score, Balthazar CT score, CRP, fecal bacterial species and DNA fingerprint profiles as well as the potentially pathologenic organisms in nasogastric aspirate were determined on the day of admission and on the 8 day. The intestinal permeability was assessed by measurement of the ratio of lactulose/rhamnose on the day of admission and on days 5 and 8. The rate of organ failure, septic complications and death cases were evaluated at the 8 day. Results: Following 7 days treatment, 38.9% patients in the EIN group were colonized with multiple organisms compared to 73.7% in the PN group (Po0.01), and 30.6% patients in the EIN grew potentially pathogenic organisms compared to 50% patients in PN group (Po0.05). The fecal bacterial DNA fingerprint profiles were less, the amount of lactobacteria and bifydobacteria decreased, and the amount of enterococci increased in PN group as compared with EIN group, Po0.05. By day 8, the lactulose/rhamnose ratio in EIN group were lower than that in PN group at days 5 and 8, Po0.05. The patients with LP got a better clinical outcomes as compared with the patients with PN. Conclusion: EIN enteral feeding can attenuate disease severity, improve the intestinal permeability and clinical outcomes.