Objective To evaluate the protective effect of omega-3 fish oil on the intestinal mucosal barrier with severe acute pancreatitis (SAP).Methods Forty Six SAP patients were enrolled (23 patients in each group) and received total parenteral nutrition (TPN) for 6 days,providing 0.8 g/(kg· d)soybean oil +0.2 g/(kg·d) ω-3 FAs based fat (FO group) or 1.0 g/(kg·d) standard soybean-oil based fat (SO group).The levels of plasma endotoxin,D-lactate and serum I-FABP expression were measured before and 7 days day after TPN.Results Forty-six patients included had significantly higher plasma level of endotoxin and D-lactate,and higher serum I-FABP concentration in the first 72 h (P > 0.05).At 7th day aforementionged indexes were significantly decreased in all SAP patients.Gastrointestinal function score,plasma endotoxin and D-lactate,and serum I-FABP concentrations in FO group were significantly lower than in SO group (P < 0.05,1.61 ± 0.79 vs.2.02 ± 0.68 ; 0.24 ± 0.15 vs.0.42 ± 0.11 ; 2.89 ±1.23 vs.3.95 ± 1.17 ; 77.5 ± 38.4 vs.100.5 ± 42.8).Conclusion Omega-3 fish oil supplementation reduces plasma endotoxin and D-lactate,and serum I-FABP concentrations,protects the intestinal mucosal barrier,and thereby decreases intestinal mucosal permeability in SAP. Key words: Acute pancreatitis; Omega-3 fish oil; Intestinal mucosal barrier