Abstract：Objective To investigate the potential effect of high mobility group box 1 protein (HMGB1) on host immune response and its molecular regulation mechanism as well as its interventional pathway following major burns/trauma. Methods With both animal experiments and clinical investigation, serial studies were conducted to observe the effects of HMGB1 on changes in immune function of T lymphoeytes, dendritic cells, and macrophages both in vivo and in vitro. Results It was found that thermal injury or trauma induced a delayed and persistent increase in HMGB1 expression as well as its release in various tissues.HMGB1 formation could markedly influence the cell-mediated immunity, including the changes in T lymphocytes, dendritic cells, and macrophages following major trauma or burns. These effects were closely related with dysfunction of various organs in the course of sepsis. Conclusion These data proved that HMGB1 not only acts as a novel "late" inflammatory mediator but is also closely associated with immunosuppression after acute insults. HMGB1 might play an important role in inducing systemic inflammatory response together with host immunological dissonance, resulting in the development of septic complications. Intervention of HMGB1 expression and release presumably provides a potentially effective way to regulate both excessive inflammatory and immune response, thereby as a measure to improve the prognosis of severe sepsis secondary to major trauma. Keywords：trauma; burn; high mobility group box 1 protein; immune function; sepsis