Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by progressive destruction of the small intrahepatic bile ducts with the formation of epithelioid granulomas. In this review, we will focus on the pathogenesis of bile duct lesions with an emphasis on periductal granulomas and microbial materials in the liver. Monocyte chemotactic proteins (MCP) -2 and -3, the most potent monocyte chemo-attractants, are expressed in the periductal area infiltrated by mononuclear leukocytes and the periphery of epithelioid granulomas. CDld, which can present lipid antigens to surrounding immune cells, is expressed in small bile duct epithelia and the periphery of epithelioid granulomas in a majority of liver with PBC but not in control livers without bile duct loss. MCP-2,-3, and CDld may be involved in the development of epithelioid granulomas and the presentation of antigens in PBC. Lipoteichoic acid (LTA) is often observed not only in bile but also in mononuclear cells of the portal tracts as well as epithelioid granulomas, whereas lipid A, a component of lipopolysaccharide (LPS), is frequently detectable on the small bile ducts in PBC. Immunodetection of LTA and LPS indicate the participation of microbial materials may contribute to the development of bile duct damage in PBC. Because permeability of the bile duct epithelium in PBC was markedly increased, the toxic substances in the bile can leak into the peribiliary space of the portal tracts consequentially. Intrabiliary substances with high antigenicity such as LTA or LPS may leak into portal tracts and activate sequentially peribiliary antigen-presenting cells (APC) such as dendritic cells and macrophages. Activated APC with various chemokines expression play an important role for more mononuclear cells infiltration. This persistent recruitment system of inflammatory cells may be a pathogenesis of persistent ductal damage and granuloma formation in PBC.