Aims: S100 beta (S100B), a member of Ca2+-modulated proteins, not only regulates various intracellular activities through stimulating inflammatory responses, but functions extracellularly as a ligand to interact with the receptor for advanced glycation end products RAGE). The expression and activation of RAGE is associated with progression of chronic liver diseases. Therefore, we investigated S100B expression and its interaction with RAGE during hepatofibrogenesis in animal model using common bile duct ligation (BDL). Methods: BDL was performed in 8-week-old male C57BL/6 mice with sham control (n=26) and BDL (n=26) groups. At week 1 and 3, hepatic fibrosis was evaluated by Sirius Red staining histologically and mRNA levels of fibrosis markers. S100B expression levels were measured by real time PCR, immunoblotting and immunohistochemistry. RAGE expression and interaction with S100B were identified by immunobloting and immunofluorescence, respectively. Results: BDL induced noticeably periportal fibrosis and bile duct proliferation. On immunoblotting, S100B expression levels were increased by 1.6 and 2.5-fold at week 1 and 3, respectively, compared with sham (P < 0.05). S100B mRNA was likewise increased by 1.98 and 2.98-fold in BDL at each time point. In immunohistochemistry, S100B was mainly detected in the bile duct epithelial cells in both sham and BDL livers. Meanwhile, RAGE expression levels on immunoblot were increased by 1.52 and 1.59-fold at week 1 and 3, respectively, compared with sham (P < 0.05). In immunofluorescence, S100B expression in bile duct epithelial cell was confirmed by co-labelling with CK-19. On merging, its distribution was corresponded with RAGE which was also merged with α- smooth muscle actin of hepatic stellate cell specific marker. Conclusions: S100B, mainly expressed in bile duct epithelial cells, was upregulated by BDL and interacted with RAGE during hepatofibrogenesis. It suggests that the intra- and extracellular functions of S100B may contribute to hepatofibrogenesis via RAGE .