In a rat tolerogenic orthotopic liver transplantation (OLT) model, recipient serum after OLT (post-OLT serum) has been reported to prevent allograft rejection. A previous proteomic study indicated that apolipoprotein E (apo-E), which is an important factor for cholesterol transportation, is expressed at the latter tolerogenic phase after OLT. It has also been known that adipose tissue-derived adipokine, adiponectin, is an essential factor for fatty acid catabolism. This study aimed to characterize the role of lipid transfer/metabolic proteins in liver transplantation tolerance.To identify the apo-E and adiponectin in post-OLT serum, Western analyses and enzyme-linked immunosorbent assay (ELISA) were performed, respectively. The immunosuppressive activities of those factors were evaluated by inhibition of the mixed lymphocyte reaction (MLR).Western analyses showed that the mobility of apo-E was shifted at the latter tolerogenic phase after OLT in a natural tolerance model, and a similar phenomenon was confirmed in the serum of a drug-induced tolerance model (rejection model+cyclosporin A (CsA); 0 to 14 days) after cessation of CsA. Further study revealed that neutralization of modified apo-E in post-OLT serum reduced the immunosuppressive activity. Additionally, plasma adiponectin was significantly elevated at the latter phase after OLT, and possessed MLR-inhibitory activity.These results suggest that the mobility shift of apo-E and/or the up-regulation of adiponectin may be necessary for overcoming the rejection, recovering the liver allograft function, and following tolerance induction in experimental OLT models, and may be useful as one indicator to surmise the prognosis after liver transplantation.