Angiotensin-converting enzyme 2 (ACE2) is the carboxypeptidase that degrades angiotensin II (Ang II) and improves the pathologies of cardiovascular disease and acute respiratory distress syndrome (ARDS)/acute lung injury. B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice and ameliorates hypertension and heart failure (Nat Commun. 2020). Here we show the therapeutic effects of B38-CAP on acute lung injury induced by abdominal sepsis, acid aspiration, or SARS_CoV2 infection. ACE2 expression was downregulated in the lungs of hamsters with SARS-CoV2 infection, or the lungs of mice with cecal ligation puncture (CLP)-induced sepsis or acid-induced lung injury thereby leading to upregulation of Ang II levels. Intraperitoneal injection of B38-CAP decreased Ang II levels and suppressed the pathologies of lung inflammation, improved lung dysfunction, and downregulated elevated cytokine mRNA levels in acute lung injury in these animal models. Thus, systemic treatment with an ACE2-like enzyme might be a potential therapeutic strategy for patients with severe sepsis or ARDS (Nat Commun. 2021; PLoS One. 2022).