Our study is the first to provide evidence suggesting that rACE2 is effective treating SARS-CoV-2 RBD protein-aggravated LPS-induced ALI and presents a molecular explanation that the ACE2-AngII-AT1R-NOX1/2 axis is associated with SARS-CoV-2 RBD protein-aggravated LPS-induced ALI. Here, NOX1 is linked to acute respiratory distress syndrome.