Background Intrahepatic biliary lithiasis is a benign biliary disease with complex pathological changes, high recurrence rate and difficult to cure. The pathological mechanism underlying hepatolithiasis development is closely related to chronic inflammation of intrahepatic bile duct and aberrant expression of mucin5ac (MUC5AC). The present study aimed to verify the up-regulation effect of IL-19 to MUC5AC in hepatolithiasis. Results He staining, PAS staining, immunohistochemistry and immunofluorescence were used to detect the expression of MUC5AC and IL-19 in bile duct tissue. The expressions of MUC5AC and STAT3 in bile duct tissue, epithelial cells and cell supernatant were detected by Western blot, PCR and ELISA. Chip experiment verified the binding of STAT3 to MUC5AC promoter sequence. The regulation effect of the stat3 signaling pathway was examined by stat3 siRNA transfection and using cryptotanshinone (CRY, a stat3 inhibitor ). MUC5AC secretion level were significantly increased in mucosa of hepatolithiasis tissue compared to controls. After pretreatment with rhIL-19, the expression level of MUC5AC in HEiECs was significantly up-regulated. Knockdown of IL-20R or pretreatment with CRY attenuated the up-regulation effect of IL-19 to MUC5AC. Conclusions The present study suggest that the IL-19 can induce MUC5AC overproduction in hepatolithiasis via stat3 pathway. Intervention of IL-19 and its downstream molecules may provide support for the treatment and prevention of hepatolithiasis.