Background Dendritic cells (DC) transfected with interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) enhance T cell immunity and tolerance. However, no quantitative studies have investigated the suppressive functions of immature dendritic cells (imDC) co-transfected with IL-10 and TGF-β1. Methods: Effects of imDC co-transfected with IL-10 and TGF-β1 (IL-10-TGF-β1-imDC) on immune tolerance induction in a rat transplantation model were investigated. In addition, effects of IL-10-TGF-β1-imDC relative to IL-10 transfected imDC (IL-10-imDC) and TGF-β1-transfected imDC (TGF-β1-imDC) were compared. Results: The infusion of IL-10-TGF-β1-imDC into recipients prolonged liver graft survival, which were sustained for more than 90 days. IL-12 serum levels decreased, whereas alanine transaminase (ALT) and total bilirubin (TBIL) slightly increased in rats infused with IL-10-TGF-β1-imDC when compared to the IL-10-imDC and TGF-β1-imDC groups. Furthermore, a higher percentage of TUNEL positive cells were observed and histological analysis of the allografts indicated a rejection activity index (RAI) of mild acute rejection. Conclusion: Our results suggest infusion of IL-10 and TGF-β1 co-transfected imDC induces alloantigen-specific T cell hypo-responsiveness, inhibits antigen-specific immunological responses to liver allografts, prolongs liver allograft survival, and enhances the immune tolerance. This approach may provide a promising and alternative for enhancing donor-specific tolerance during liver transplantation.