This study was designed to explore the effect of up-regulation of interleukin(IL)-37a expression on lung function and T helper type 1(Th1)/Th2 cytokine balance in rats with acute respiratory distress syndrome(ARDS).Mesenchymal stem cells(MSCs)overexpressing IL-37a were constructed and co-cultured with mononuclear cells,then flow cytometry was used to detect the effect of IL-37a overexpression on Th1 and Th2 expression,and ELISA was used to detect IFN-γ and IL-4 levels in supernatant of the culture medium.Total of 30 SD rats were recruited and randomly divided into control group(sham surgery),ARDS group(lipopolysaccharideinduced establishment of ARDS model),and IL-37a group(ARDS model+tail vein injection of 10 μg/kg IL-37a),with 10 rats in each group.After 12 hours of modeling,arterial oxygen pressure(PaO2)and oxygenation index(PaO2/FiO2)were measured using a blood gas analyzer,and the dry/wet(W/D)ratio of the lungs was measured.HE staining was used to observe lung tissue pathology and evaluate lung pathological injury scores;ELISA was used to detect alveolar lavage fluid(BALF)and serum IL-4 and IFN-γ expression;flow cytometry was used to detect spleen Th1/Th2;while Western blot was used to detect the protein expression of NF-κB and NLRP3 in lung tissue.Data showed that the levels of Th1,Th1/Th2,and IL-4 in the peripheral cells of the overexpression IL-37a group were lower than those in the negative control group cells,while the expression of Th2 and IFN-γ were higher than those in the negative control group cells(P＜0.05).Compared with the control group,the ARDS group showed lower levels of PaO2,PaO2/FiO2,BALF and serum IL-4,but higher levels of W/D,lung pathological injury score,BALF and serum IFN-γ,spleen Th1/Th2,and lung tissue NF-κB and NLRP3 proteins.IL-37a could reverse the changes mentioned above in ARDS rats(P＜0.05).Taken together,up-regulation of IL-37a expression can ameliorate lung injury in ARDS rats,which may be related to the role of IL-37a in inducing MSC differentiation and promoting the restoration of Th1/Th2 balance.