Phosgene-induced lung injury is an important type of acute lung injury (ALI). Currently, no effective clinical treatment has been developed yet. Our previous study revealed that expressions of 6 miRNAs were significantly increased in phosgene-induced lung injury. The screened miRNA with the most significant effect on hepatocyte growth factor (HGF) expression by mesenchymal stem cells (MSCs) was transfected into MSCs. This study aimed to investigate whether the transfected MSCs had better therapeutic effects than MSCs alone. MSCs were co-cultured with miRNA mimics for 24h and 48h. HGF expression in culture supernatant was detected by ELISA. HGF expression in MSCs was detected by Western blot after being co-cultured with the selected miRNA inhibitor. The transfected MSCs were given to rats suffering from phosgene-induced lung injury. Expressions of TNF-alpha, IL-6, IL-beta and IL-10, were assayed by ELISA. SP-C mRNA level was tested by RT-PCR. VE-CAD expression was tested by Western blot. We found that miRNA-378a-5p most increased HGF expression among the six miRNAs. After transfection of MSCs with miRNA-378a-5p inhibitor, HGF expression was decreased. Compared with untreated MSCs, MSCs transfected with miRNA-378a-5p exhibited more significant decreases in lung injury score, white blood cell count and protein content while restoring respiratory indexes. Meanwhile, expressions of TNF alpha, IL-6, IL-beta were decreased while those of IL-10, SP-C and VE-cadherin were increased. In conclusion, MSCs transfected with miRNA-378a-5p were more effective in treating phosgene-induced lung injury by repairing the secretion of alveolar epithelial cells and improving the permeability of vascular endothelial cells compared with MSCs alone. (C) 2020 Elsevier Inc. All rights reserved.