The anti-inflammatory role of miR-23b-3p (miR-23b) is known in autoimmune diseases like multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. However, its role in sepsis-related acute lung injury (ALI) and its effect on macrophages in ALI remain unexplored. This investigation aimed to evaluate miR-23b's therapeutic potential in macrophages in the context of ALI. The study found reduced miR-23b expression in macrophages within ALI tissue. Intratracheal delivery of miR-23b mimics alleviated ALI by partially inhibiting M1 macrophage activation through the Lpar1-NF-κB pathway. Effective delivery systems are crucial for prolonging miR-23b activity in the lungs, reducing dosage, and minimizing side effects by specifically targeting macrophages. However, current vector systems for nucleic acid delivery, including viral, lipid-based, polymer-based, and peptide-based vectors, face limitations due to eliciting immune responses. Exosomes have garnered significant attention as a leading gene delivery system due to the safety, effectivity and low immunogenicity. We further isolated exosomes from bone marrow-derived mesenchymal stem cells, modified exosomes with mannosylated ligands to enhance the targeted delivery of miR-23b to macrophage. This approach represents a promising novel therapeutic strategy for treating sepsis-induced ALI.