Tight junctions of hepatocytes play crucial roles in the barrier to keep bile in bile canaliculi away from the blood circulation, which we call the blood-billiary-barrier (Kojima et al., 2003). Tight junction proteins of hepatocytes are regulated by various cytokines and growth factors via distinct signal transduction pathways. They are also considered to participate in signal transduction pathways that regulate epithelial cell proliferation, gene expression, differentiation and morphogenesis. This review focuses on recent findings about the relationship between tight junction proteins and signal transduction pathways in hepatocytes.