The sepsis and sepsis-induce lung injury threats seriously human health. Dexmedetomidine (DEX), a sedative drug, plays an active role in preventing sepsis-induced lung injury during the basic and clinical practice. The current article reviews the role and mechanism of DEX dexmedetomidine alleviating sepsis-induced lung injury from the aspects of inflammation, oxidative stress, apoptosis, mitochondrial dynamics, autophagy, vascular permeability, neuro-regulation, targeting miR-128-3p/MAPK14 and DNA methylation, etc. This review looks forward to deepen the understanding the application of DEX in the field of critical care medicine, expand the pharmacological effect of DEX and provide a new idea for the prevention and treatment of sepsis from the sedation approach.