The polycystic kidney (PCK) rat shows multiple segmental and saccular dilatations of the intrahepatic bile ducts associated with portal fibrosis, and is an orthologous rodent model of Caroli?s disease with congenital hepatic fibrosis as well as autosomal recessive polycystic kidney disease. A cholangiocyte cell line that retains properties of the biliary epithelium lining the bile ducts in vivo has been developed from the PCK rat, and it has provided a novel in vitro system to study the mechanisms of biliary cystogenesis. In particular, the 3-D culture system is useful to explore the effects of therapies on biliary cystogenesis. Studies using the PCK rat and cultured cholangiocytes have revealed that the biliary dysgenesis is associated with cholangiocyte hyperproliferation, cell-matrix interactions and accelerated fluid transport. The levels of cAMP and intracellular calcium in the cholangiocytes are closely associated with the cyst pathogenesis, and several key signaling pathways such as the activation of B-Raf/MEK/ERK signaling pathway have been identified. This article reviews the advances in therapeutic approaches aiming for ameliorating the hepatobiliary lesions of the PCK rat, particularly focusing on those for the biliary cystogenesis.