Objective To explore the changes of nuclear factor-κB (NF-κB) activity, TNF-α, IL-1β and IL-10 contents in the lung tissue of rabbit with seawater drowning-induced acute lung injury (SWD-ALI) and the effects of dexamethasone on the changes. Methods Forty-two New Zealand white rabbits were randomly allocated to control group (C group, n=18), seawater drowning group (S group, n=12) and dexamethasone treatment group (D group, n=12). The drowning model was established by instilling seawater (2 ml/kg body weight) into the endotracheal catheter of animals, then the rabbits received arterial injection of dexamethasone (D group, 1 mg/kg body weight) or 2 ml normal saline (S group). Blood gas analysis was done at predefined time points. The lung wet to dry weight ratio (W/D) and lung permeability index (LPI) were calculated. The activity of NF-κB was analyzed by non-radioactive electrophoretic mobility shift assay (EMSA). The contents of TNF-α, IL-1β and IL-10 were detected by ELISA. Meanwhile, the pathology changes of lung tissues were detected by H-E staining, and the semi-quantitative lung pathologic scores (LPS) was also calculated. Results The lung of rabbits in S group was obviously enlarged and had more severe edema and congestion compared with C group; furthermore, histopathologic findings indicated inflammatory cell infiltration and other pathologic signs of ALI; the oxygenation index (PaO2/FiO2) reached the bottom at 0.5 h and did not elevate to more than 300 mmHg(1 mmHg=0.133 kPa) until 6 h. The largest W/D ratio appeared at 3 h after seawater drowning, and the highest LPI and LPS appeared at 6 h; and NF-κB activity and the contents of TNF-α, IL-1β and IL-10 in lung tissues were significantly higher in S group than in C group（P<0.05,P<0.01）. The pathological changes of lung in the rabbits of D group were improved compared with S group but worse than those of group C. The W/D ratio, lung permeability index, and lung pathological score in D group were lower than those of the S group; and the oxygenation index was greatly improved 6 h after seawater drowning. NF-κB activity and the contents of TNF-α, IL-1β and IL-10 in lung tissues were significantly lower than those of the S group（P<0.05,P<0.01）. Conclusion Dexamethasone can inhibit the activity of NF-κB and the expression of TNF-α, IL-1β and IL-10 in the lung tissue of rabbits with SWD-ALI and relieve the inflammatory responses and pathological changes.