Cholangiocarcinoma (CCA) is a malignant neoplasm affecting thousands of individuals worldwide. CCA develops through a multistep process. In the current study, an oral thioacetamide (TAA)‑induced model of rat CCA was established which generates the histological progression of human CCA, particularly the mass‑forming type. Seven male Sprague‑Dawley rats were treated with TAA for 24 weeks to induce CCA. Following the generation of the rat CCA model, whole rat genomic oligo microarray was performed to examine gene expression profiles in CCA and non‑cancerous liver samples. In brief, 10,427 genes were found to be differentially expressed (8,318 upregulated and 3,489 downregulated) in CCA compared with non‑tumor liver tissue. The top 50 genes (upregulated or downregulated) were selected and their functional involvement in various pathways associated with cancer progression was analyzed, including cell proliferation, apoptosis, metabolism and the cell cycle. In addition, increased expression of CLCA3, COL1A2, DCN, GLIPr2 and NID1, and decreased expression of CYP2C7 and SLC10A1 were validated by quantitative real‑time PCR. Immunohistochemical analysis was performed to determine the protein expression levels of GLIPr2 and SLC10A1. The gene expression profiling performed in this study provides a unique opportunity for understanding the carcinogenesis of TAA‑induced CAA. In addition, expression profiling of a number of specific genes is likely to provide important novel biomarkers for the diagnosis of CCA and the development of novel therapeutic strategies for CCA.