This work aimed at studying the effect of early enteral nutrition (EN) on serum endotoxin and intestinal permeability in patients with severe acute pancreatitis. 70 cases of patients with severe acute pancreatitis were cured in our hospital from April 2015 to January 2016. Patients selected were randomly divided into two groups including a group of patients having parenteral nutrition (group PN) and that had enteral nutrition (group EN). The results were assessed by: 1) the differences of serum endotoxin level; 2) the differences of the lactulose/mannitol ratio of urine, before intervention and one and two weeks after the intervention. Before the intervention, both groups had similar levels of serum endotoxin and the same lactulose/mannitol excretion rate of urine (p>0.05). One and two weeks after the intervention, the serum endotoxin level and the lactulose/mannitol excretion rate of urine of the group PN were significantly higher than the group EN (p<0.05). Compared with PN, EN has a bigger effect on serum endotoxin and intestinal permeability in patients with severe acute pancreatitis. EN can better promote the elimination of serum endotoxin and reduce intestinal permeability. Therefore, EN deserves clinical expansion.