Objective To study the expression of interleukin (IL)-37 and related factors in lung tissue of rats with acute lung injury, and explore the role and significance of IL-37 in acute lung injury so as to understand the pathogenesis of acute lung injury. Methods Forty-five clean-grade Wistar rats were randomly divided into a healthy control group, a bleomycin group and a dexamethasone treatment group, with 15 rats in each group. The rats in the bleomycin group and the dexamethasone group were treated with bleomycin at a dose of 4 mg/kg by intratracheal administration. The healthy control group was given the same volume of saline as control. The dexamethasone treatment group was injected with dexamethasone 3 mg/kg intraperitoneally twice a day on the basis of acute lung injury. The healthy control group and the bleomycin group were injected intraperitoneally with normal saline as control. The rats in each group were sacrificed at 7, 14 and 28 days after modeling. The histopathological changes of lung tissue were evaluated by HE staining. The levels of IL-37 in lung homogenate and tumor necrosis factor (TNF)-α in serum were measured. The expression of IL-18 mRNA in lung tissue was detected by RT-PCR. Results Pathological morphology showed that the lung tissue of the healthy control group was complete, no inflammatory and fibrotic changes at all time points. The lung tissues of the bleomycin group and the dexamethasone group manifested with acute alveolitis firstly and thus developed fibrosis changes lately, and the changes in the dexamethasone group were more slightly than those in the bleomycin group. The contents of IL-37 and TNF-α and the expression of IL-18 mRNA in the bleomycin group and the dexamethasone group reached to the highest point on the 7th day, and then decreased, but were significantly higher than those of the healthy control group on the 28th day (all P<0.05). Conclusions IL-37 plays an important role in the pathogenesis of acute lung injury in rats. This effect may be related to the regulation of IL-18 and TNF-α transduction.