Abstract: Objective To observe the effects of docosahexaenoic acid (DHA) on the expressions of TNF–α, IL–6, and leukotriene B₄ (LTB₄) in serum and expression of NF–κB in pulmonary tissue of rats with severe scald injury. Methods One hundred and sixty SD rats were divided into sham injury (A), sham injury+ DHA (B), scald (C), and scald+ DHA (D) groups according to the random number table, with 40 rats in each group. Rats in groups A and B were sham injured, while rats in groups C and D were inflicted with 30% TBSA full–thickness scald on the back. Rats in groups B and D were injected with 0.5 mg/mL DHA solution with the dosage of 1 mL/kg via tail vein 5 minutes post injury, while rats in groups A and C with normal saline solution 1 mL/kg. At post injury hour (PIH) 3, 6, 12, 24, and 48, pulmonary tissue and abdominal aorta blood were collected from 8 rats in each group. The serum levels of TNF–α, IL–6, and LTB₄ were determined with ELISA, and the protein expression of NF–κB p65 in pulmonary tissue was determined with Western blotting. Data were processed with analysis of variance of factorial design and LSD–t test. Results (1) The serum levels of TNF–α and IL–6 of rats in group A were similar to those of group B at each time point (with t_TNF–α values from 0.223 to 0.947, t_IL–6 values from 0.767 to 2.084, P values above 0.05). Compared with those of group A, the serum levels of TNF–α and IL–6 of rats in groups C and D were significantly higher at each time point (with t_TNF–α values from 11.800 to 40.357, t_IL–6 values from 10.334 to 39.321, P values below 0.01). The serum levels of TNF–α and IL–6 of rats in group D were significantly lower than those of group C at each time point (with t_TNF–α values from –17.643 to –8.331, t_IL–6 values from –21.596 to –6.332, P values below 0.01). The serum levels of TNF–α and IL–6 in groups C and D both showed a trend of increase earlier and decrease later, and they peaked at PIH 12, respectively (360.4±13.2), (306.8±7.2) pg/mL and (265.4±12.3), (230.5±2.2) pg/mL. (2) The serum level of LTB₄ in group A was similar to that of group B at each time point (with t values from 0.787 to 1.096, P values above 0.05). The serum level of LTB₄ was significantly higher in groups C and D than in group A at each time point (with t values from 7.501 to 38.962, P values below 0.01). The serum level of LTB₄ in group D was obviously lower than that of group C at each time point (with t values from –19.244 to –2.532, P values below 0.01). The serum level of LTB₄ in groups C and D both showed a trend of increase earlier and decrease later, and it peaked at PIH 12, (4.59±0.29) and (2.85±0.32) ng/mL respectively. (3) The protein expression of NF–κB p65 in pulmonary tissue in group A was similar to that of group B at each time point (with t values from 0.847 to 1.256, P values above 0.05). The protein expression of NF–κB p65 was significantly higher in groups C and D than in group A at each time point (with t values from 15.167 to 98.074, P values below 0.01). The protein expression of NF–κB p65 in group D was obviously lower than that of group C at each time point (with t values from –37.190 to –14.415, P values below 0.01). The protein expression of NF–κB p65 in groups C and D both showed a trend of increase earlier and decrease later, and it peaked at PIH 12, respectively 4.46±0.12 and 2.94±0.21. Conclusions Parenteral supply of DHA to rats with severe scald injury can reduce the levels of TNF–α, IL–6, and LTB₄ in serum and decrease the expression of NF–κB in pulmonary tissue, thus alleviating the inflammation response.