Besides differentiating into multiple mesenchymal tissues, bone marrow mesenchymal stem cells(BMMSCs) can also develop into hepatocyte-like cells in vitro and in vivo. CTLA4Ig-gene modified BMMSCs have a strong immunosuppressive function cultured in both normal and hepatic differentiation medium and this gene modification improves the biological function of BMMSCs. Recombinant adenovirus containing CTLA4Ig gene was constructed, and transferred into rat BMMSCs in vitro. The transfected BMMSCs, cultured in hepatic differentiation medium containing HGF for 14 days, could express hepatocyte-specific markers including AFP, Alb and CK18, and these differentiated cells from BMMSCs also had the capabilities of glycogen deposition and ICG uptake and excretion, which are hepatocyte-specific functions. Expression of CTLA4Ig in the transfected BMMSCs cultured in the normal growth medium or the differentiation medium was confirmed by RT-PCR, Western blot and fluorescent immunocytochemistry, and the expression at 14 d was weaker than that at 7 d. In the model of MLR, the transfected BMMSCs could suppress immune response, and the suppression was statistically stronger than that of BMMSCs at the same number. Even if cultured in hepatic differentiation medium, the transfected BMMSCs also had the same immunosuppression function. In rat liver transplantation model, the CTLA4Ig-gene modified BMMSCs infused into liver graft after operation could prolong the survival time of the recipients. Adenovirus-mediated CTLA4Ig gene transfer into BMMSCs can not change the potential of BMMSCs to differentiate into hepatocytes, and on the other hand, this gene transfer can improve the immunosuppressive function of BMMSCs, which can broaden the applying space of BMMSCs in the clinical therapy for liver diseases.