〔Abstract〕 Objective To determine expression profile of VISTA on lymphocyte and the potential regulatory effects on immune response in a murine model of sepsis. Methods Expression profile of VISTA on T lymphocytes in the spleen and peripheral blood was examined. Mice wereintravenously injected with an agonistic VISTA mAb(MH5 A) or isotype control, and then the survival rate, cytokine expression, bacterial burden and lymphocyte apoptosiswere determined. Results VISTA was substantially expressed on T cell from the spleen and peripheral blood, septic peritonitis did not induce significant changes in the expression profiles at 24 h post surgery(P>0.05 in each comparison). Treatment with MH5 A improved the survival of septic mice(8/12vs2/12,P=0.01), accompanied by reduced lymphocyte apoptosis [(30 123±6 400)vs(45 482±8 652),P=0.03], decreased bacterial burden and lessened cytokines expression, such as TNF-α, IL-6, IL-1β and IFN-γ(P<0.05 in each comparison). Conclusion The present study identified VISTA as a novel immune checkpoint in the regulation of T cell apoptosis and inflammatory response during sepsis. VISTA agonism might offer a promising approach in the immunotherapy for sepsis.