Highlights • Both LXs and RAAS could regulate inflammatory response, oxidative stress, fibrosis, besides proliferation and apoptosis. It seemed the biological effects of renin angiotensin-aldosterone system (RAAS) and Lipoxins (LXs) are similar. The roles of RAAS in chronic disease is more apparent, and we had reported that BML-111(a lipoxin receptor agonist) equilibrated ACE-AngII-AT1R and ACE2-Ang-(1–7)-Mas axis to protect chronic disease hepatic fibrosis in rats. But its role in acute injury is less studied. • In this paper, acute models were used to observe the relations of RAAS and LXs in acute liver/lung injury. The results demonstrated that BML-111 could improve acute liver/lung through regulating RAAS. • BML-111 can protect not only chronic disease but also acute injury via regulating RAAS.RAAS might be novel and potential targets for LXs/analogs against acute and chronic diseases. Abstract Background The renin angiotensin-aldosterone system (RAAS) and lipoxins (LXs) have similar roles in many processes. We previously reported that BML-111, a Lipoxin receptor agonist, inhibited chronic injury hepatic fibrosis by regulating RAAS, but whether LXs are involved in BML-111-mediated protection from acute injury is unclear still. Methods We established models of acute liver/lung injury and confirmed them with histopathology and myeloperoxidase (MPO) measurements. BML-111, a lipoxin receptor agonist, was applied to mimic the effects of LXs. The contents and activities of angiotensin converting enzyme(ACE) and angiotensinconverting enzyme 2 (ACE2) were measured through ELISA and activity assay kits respectively. Angiotensin II (AngII), angiotensin-(1–7) (Ang-1–7), AngII type 1 receptor (AT1R), and Mas receptor were quantified with ELISA and Western blot. Results Models of acute injury were established successfully and BML-111 protected LPS-induced acute lung injury and LPS/D-GalN-induced acute liver injury. BML-111 repressed the activity of ACE, but increased the activity of ACE2. BML-111 decreased the expression levels of ACE, AngII, and AT1R, meanwhile increased the levels of ACE2, Ang-(1–7), and Mas. Furthermore, BOC-2, an inhibitor of lipoxin receptor, reversed all the effects. Conclusion BML-111 could protect against acute injury via regulation RAAS. [ABSTRACT FROM AUTHOR]