Background: CD256 and CD257 belong to the TNFSF (Tumor necrosis factor superfamily), share closest homology structure, and can form functional heterotrimers. They may be involved in the progression of SLE (Systemic lupus erythematosus), RA (Rheumatoid arthritis), and other autoimmune disorders. In this present study, CD256 and some related molecules were detected and were investigated regarding the potential role of the CD256 signal during the development of renal allograft rejection. Methods: In 2009, 46 cases of renal allografts were collected, excised for evaluation of dysfunction, and 10 renal protocol biopsies with normal renal function were controlled. Immunohistochemistry (IHC) staining was applied to detect CD256, CD257, C4d, CD138 and other related molecules. HistoQuest Analysis software and SPSS16.0 were used to read and analyse the results. Results: Pathological diagnosis was made according to Banff 2005 guidelines: antibody-mediated rejection (ABMR) 15 cases, T-cell-mediated rejection (TCMR) 16 cases, and 15 unknown aetiology cases (UAC). IHC results showed that CD256, CD257, and receptors for B cell activating factor receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator calcium modulator, and cyclophilin ligand interactor (TACI) were expressed on the membrane/cytoplasm of renal tubular epithelial cells (RTEC) in the ABMR and TCMR group, while these molecules were not or weakly expressed in UAC and protocol biopsies. CD257 strong staining could be seen in ABMR, CD256 strong staining in both BCMR and TCMR, and there was statistical significance compared with other groups (p<0.05). The receptors BAFF-R, BCMA, and TACI all strongly stained in ABMR, TACI also stained strongly in TCMR, and there was statistical significance compared with other groups (p<0.05). The CD138(+) molecule could be found in the renal interstitium and membrane/cytoplasm of RTEC, the CD138 mean expression in ABMR was statistically higher than other groups (p<0.05). The correlation analysis indicated that CD256 significantly correlated with BCMA, TACI, and CD138, while CD257 significantly correlated with BAFF-R, BCMA, TACI, and CD138. Conclusions: CD256 can be found in ABMR tissues and may participate in the progression of ABMR together with CD257. (Clin. Lab. 2012;58:411-418)