In addition, the results showed that overexpression of PIK3R2 could reverse the effects of EGFR@CXCL8@exo-miR-126a-3p on macrophage polarization and NLRP3 signaling pathway and ferroptosis, indicating that EGFR@CXCL8-exo-miR-126a-3p inhibited LPS-induced macrophage polarization and NLRP3 signaling pathway and ferroptosis by targeting PIK3R2 to alleviate ALI. Here, CXCL8 is linked to acute respiratory distress syndrome.