Histone is a kind of basic structural protein of eukaryotic chromatin. When cells is damaged or necrotic, the histone proteins were released into the extracellular space and become extracellular histone proteins. Recent studies have found that extracellular group proteins play an important role in ischemic/reperfusion injury(I/RI) in the lungs. This review summarized the studies of recent years about the role of histone in I/RI in the lung and provided references for further studying the role and mechanism of histone in I/RI. Elaborating the structure and biological functions of histone and the source of the extracellular histone to investigate the possible role of the extracellular histone and the underlying mechanism of histone regulation in the I/RI in many aspects: such as toxicity, nod-like receptor protein 3 (NLRP3) pathway, injured polysaccharide-coated pathway, associated inflammatory signaling pathways, and platelet-dependent pathways, etc. Further studies of histone would provide new therapeutic target for the clinical treatment of ischemia/reperfusion injury.