Abstract: Objective To observe the effects of ω-3 polyunsaturated fatty acids (PUFA) on damage of intestinal mucosa of rats with severe burn in early stage and to explore the mechanism. Methods One hundred and twenty SD rats were divided into sham injury group, pure burn group, and ω-3 PUFA group according to the random number table, with 40 rats in each group. Rats in sham injury group were sham injured, while rats in pure burn group and ω-3 PUFA group were inflicted with 30% total body surface area full-thickness scald (hereinafter referred to as burn) on the back. Rats in sham injury group and pure burn group were injected with normal saline solution (1 mL/kg) by tail vein, while rats in ω-3 PUFA group were injected with ω-3 PUFA solution (1 mL/kg) by the same way at 5 minutes post injury. At post injury hour (PIH) 3, 6, 12, 24, and 48, abdominal aorta blood and intestinal mucosa were collected from 8 rats in each group, respectively. Serum content of diamine oxidase (DAO) was detected by spectrophotography. Serum content of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) was determined by enzyme-linked immunosorbent assay. Protein expression of NF-κB-p65 in intestinal mucosa was determined by Western blotting. Data were processed with analysis of variance of factorial design, one-way analysis of variance, chi-square test, LSD test, and Bonferroni correction. Results (1) At all time points post injury, serum content of DAO of rats in pure burn group and ω-3 PUFA group was significantly higher than that in sham injury group (with P values below 0.01), and serum content of DAO of rats in ω-3 PUFA group was significantly lower than that in pure burn group (with P values below 0.01). (2) At all time points post injury, serum content of TNF-α and IL-6 of rats in pure burn group and ω-3 PUFA group was significantly higher than that in sham injury group (with P values below 0.01), and serum content of TNF-α and IL-6 of rats in ω-3 PUFA group was obviously lower than that in pure burn group (with P values below 0.01). (3) At all time points post injury, protein expressions of NF-κB-p65 in intestinal mucosa of rats in pure burn group and ω-3 PUFA group were significantly higher than those in sham injury group (with P values below 0.01). At PIH 3, 6, 12, 24, and 48, protein expressions of NF-κB-p65 in intestinal mucosa of rats in ω-3 PUFA group were 1.398±0.016, 1.999±0.948, 2.803±0.065, 1.739±0.602, and 1.484±0.645, obviously lower than 2.096±0.113, 3.402±0.189, 4.183±0.558, 3.618±0.408, and 2.614±0.775 in pure burn group (with P values below 0.01). Conclusions The ω-3 PUFA may alleviate intestinal mucosa injury of rats with severe burn in early stage through reducing protein expression of NF-κB-p65 of intestinal mucosa, serum content of DAO, TNF-α, and IL-6, and inhibiting inflammatory response.