<p>Acute lung injury (ALI) is a common clinical complication of sepsis and ferroptosis plays an important role in ALI. The aim of this study was to evaluate the effects of CD8 antibodies modified PD-1 engineered CD8⁺ T lymphocytes (CTL) membrane loaded poly lactic-co-glycolic acid (PLGA)/ferroptosis inhibitor ferrostatin-1 (Fer-1) (CD8@PD-1-CTL-M@PLGA/Fer-1) on acute lung injury (ALI). High expression PD-1 CD8 + T (CTL) was established and the membrane (PD-1-CTL-M) was extracted, CD8 monoclonal antibody modified PD-1-CTL-M was used to enhance the targeting capability of PLGA/Fer-1 nanoparticles to target CD8 + T (CTL). ALI model was established by lipopolysaccharide (LPS) with mice and CD8 + T (CTL). The results showed that CD8@PD-1-CTL-M significantly enhanced the protective effects of PLGA/Fer-1 on ALI and targetability of PLGA/Fer-1 nanoparticles on CD8 + T (CTL). The mechanism was related to CD8@PD-1-CTL-M@PLGA/Fer-1 targeting regulation of PI3K/Akt and MAPK signal pathway in CD8 + T (CTL). This study provided a new treatment method for ALI.</p> Graphical Abstract <p></p>