BACKGROUNDAllogeneic transplantation immune tolerance is currently a hot research issue and soluble CD83(sCD83) is a novel immunomodulator with great potential in inducing transplantation tolerance.OBJECTIVETo investigate the mechanism of the immune tolerance effect of sCD83 on rat liver transplantation.METHODA rat liver transplantation model was established to study the effects of sCD83 on the expression levels of IL-2, IL-10, and TGF-β in peripheral blood and the mRNA expressions of foxp3, TGF-β, and Indoleamine 2,3-dioxygenase (IDO) in liver. The expression changes of costimulatory molecules CD80, CD86, and MHC-II on the surface of DC cells and the expressions of IDO + DC cell, TGF-β + CD4 + T cell, and CD4 + CD25 + Foxp3 + T cell were analyzed and compared.RESULTSsCD83 alleviated the rejection activity index (RAI) of rat liver transplantation in the early stage, increased the expressions of TGF-β, IL-10 in peripheral blood and the mRNAs of IDO, TGF-β and foxp3 in the transplanted liver, and down-regulated the expressions of MHC-II, CD86, and CD80 in DC cells, resulting in significant increased numbers of tolerogenic TGF-β + CD4 + T cells, Treg cells, and IDO + DC cells with low expression.CONCLUSIONsCD83 inhibited acute rejection after liver transplantation in an allogeneic rat, and the mechanism was associated with the effect that sCD83 increased the expression of TGF-β, activated IDO immunosuppressive pathway, and increased tolerogenic DC cells and Treg cells.