Apoptosis plays a pivotal role in portal tract damage of primary biliary cirrhosis (PBC). Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is an apoptotic inducer, and it has been reported that the expression of TRAIL receptors is up-regulated by increased bile acid level and the serum level of soluble TRAIL (sTRAIL) is elevated in PBC patients. In the present study, we investigated the association of TRAIL in peripheral blood with the pathogenesis of PBC and chronic hepatitis B. The expression levels of TRAIL mRNA and protein on leukocytes and sTRAIL in plasma from 27 patients with PBC, 25 with CHB and 30 healthy controls were determined respectively by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR), flow cytometry (FCM) and ELISA. The expression levels of TRAIL mRNA and protein on leukocytes and plasma sTRAIL were all up-regulated in the patients with PBC and CHB compared to controls. In the two diseased groups, TRAIL mRNA showed significant correlation of both membrane-bound TRAIL (mTRAIL) on monocytes and plasma sTRAIL. So did plasma TNF-alpha. In PBC patients, mTRAIL and sTRAIL correlated well with gamma-glutamyltransferase and alkaline phosphatase, but not with aspartate aminotransferase and alanine amino-transferase. The opposite case was found in CHB patients. These results suggested that both mTRAIL and sTRAIL might be involved in the development and progression of PBC and CHB in humans, but the mechanisms might be different.