Objective To establish a thioacetamide (TAA)-induced bile duct carcinoma rat model and to observe the effect of aspirin on bile duct carcinoma by interrupting the model. Methods Sprague-Dawley (SD) male rats were given drinking water containing TAA (300 mg/L) for 5 months, and tumor formations of the livers were observed by H-E staining at the 8^th, 12^th, 16^th, and 20^th weeks, respectively. The expression of carbonic anhydrase 2 (CA-2) in liver tissues was also detected by immunohistochemistry. SD male rats were also selected and treated with aspirin after exposing to TAA for 12 weeks. And then the tumor formations of the livers were observed by H-E staining at the 3^rd and 6^th months, and the expression of CA-2 was detected by immunohistochemistry. Bile duct carcinoma cells QBC939 were obtained and treated with aspirin (0 mmol/L and 5 mmol/L), and the expression of CA-2 was detected by Western blotting after culturing for 48 h. Results Obvious fibrosis was found in the livers of some rats at 12^th weeks after exposing to TAA; large number of fibrous tissue hyperplasia and microscopic or suspected tumors were found in the livers at the 16^th weeks; visible tumors in the livers were found in all the rats at the 20^th weeks. The incidence of hepatic tumors or suspected tumors was 28.6% (2/7) in rats treated with aspirin for 6 months, while it was 100% (7/7) in rats without aspirin treatment. The expression of CA-2 in liver tissues was gradually increased with the development of bile duct carcinoma in rats, while the expression of CA-2 in liver tissues was decreased after treating with aspirin. The expression of CA-2 in QBC939 cells treated with 5 mmol/L aspirin for 48 h was significantly decreased versus the untreated control group (P<0.01). Conclusion TAA can successfully induce intrahepatic bile duct carcinoma. Aspirin can interrupt the development of bile duct carcinoma and may be used to prevent intrahepatic bile duct carcinoma.