Abstract: Objective The ventilator-induced lung injury(VILI) rat model was established in this study to explore the influence of DEX on its inflammatory response and the axis of microRNA-223-3 p/nucleotide binding oligomeric domain-like protein 3(miR-223-3 p/NLRP3). Methods The adult healthy 6-week-old Specific pathogen-free(SPF) grade male SD rats of were randomly divided into 5 groups using the random number table: control group(NC group), model group(M group), low dose DEX group(L-DEX group), medium dose DEX group(M-DEX group), high dose(H-DEX group) DEX group, 12 rats in each group; the rats were given 0.5, 2.5 and 5.0 μg/(kg·h) DEX intravenously in L-DEX group, M-DEX group and H-DEX group respectively. At the end of 4 h, the rats were sacrificed and the lung permeability index(LPI) and the ratio of lung tissue wet weight to dry weight(W/D), miR-223-3 p, NLRP3 mRNA and protein, caspase-1 protein expression and IL-1β and IL-18 levels in lung homogenate were measured. Results Compared with group M, the LPI, W/D ratio, NLRP3 mRNA(4.04±0.38, 2.12±0.32, 1.98±0.25) and NLRP3 protein(0.92±0.11, 0.58±0.06, 0.39±0.02), caspase-1 protein, IL-1β, IL-18 levels in L-DEX group, M-DEX group and H-DEX group decreased in turn, while NLRP3 mRNA in group M was 5.47±062, and NLRP3 protein was 1.31±0.27), and the level of miR-223-3 p increased in turn in the L-DEX group, M-DEX group, H-DEX group(P<0.05). Conclusion DEX may up-regulate the expression of miR-223-3 p, down-regulate the expression of NLRP3, caspase-1 and downstream inflammatory factors, which is closely related to the miR-223-3 p/NLRP3 axis, so as to reduce the VILI and inflammatory response in rats.