Sepsis is a life-threatening multi-organ dysfunction syndrome caused by an imbalanced immune response to infection. Its condition is complex and variable, and it is one of the main causes of death in intensive care unit. Lung injury is the common organ injury in sepsis patients. Macrophages are an important component of innate and adaptive immunity that can dominate immune status through different polarization types. At the early stage of sepsis, macrophages often polarize to pro-inflammatory M1-like and lead to immune hyperactivity, while convert to anti-inflammatory M2-like at the late stage, resulting in immunosuppression. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway plays an important role in the regulation of inflammatory signals, and the activation of the pathway occurs throughout the entire process of sepsis development and macrophage polarization. This review analyzes how the JAK/STAT pathway mediates the development of sepsis-associated lung injury by affecting macrophage polarization, and summarizes the potential therapeutic targets, with a view to provide new ideas for the treatment of sepsis.