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Acute respiratory distress syndrome (ARDS) is a common critical respiratory disease with a high mortality rate that has been sustained for many years and is caused by a variety of intrapulmonary and extrapulmonary pathogenic factors. However, the effective clinical interventions for ARDS currently in use mainly involve respiratory and organ support therapy, and no effective targeted drug intervention is beneficial for patients with ARDS. In the present study, GALA-PFD-Lip were constructed to reduce lung inflammation, reduce lung oxidative stress, inhibit endothelial-to-mesenchymal transition (EndMT), and reduce early pulmonary fibrosis. We found that GALA-PFD-Lip have efficacious lung targeting activity and biosafety, and the anti-inflammatory and antifibrotic effects of GALA-PFD-Lip are superior to those of pure PFD. These results suggest that GALA-PFD-Lip has good clinical translation potential for the treatment of ARDS-induced pulmonary infections. This study provides new ideas for the treatment of inflammation and for the prevention of early progressive fibrosis that is characteristic of ARDS.