Abstract: Objective: To determine the role of hypoxia in stimulating the expression of angiopoietin-2 (Ang-2) in colorectal cancer (CRC). Methods: The expression of Ang-2 and glucose transporter-1 (GLUT-1) were examined in 3 cultured CRC cell lines by reverse transcriptase-polymerase chain reaction (RT-PCR) assays and in specimens of hepatic CRC metastasis using immunohistochemistry (IHC). Results: Hypoxia-induced Ang-2 mRNA expression was observed in the HCT116 cell line that did not express Ang-2 under normoxic conditions. In the LoVo cell line, the Ang-2 mRNA was only detectable at 48 hr in hypoxic serum-deprived cultures. In the HT29 cell line, Ang-2 mRNA could be detected under both normal oxygen supply and anoxic conditions, without noticeable difference. A stepwise increase of Ang-2 expression from the periphery to the central part of liver metastatic foci was noted whereas vascular density had the reverse pattern. An expression pattern similar to that of Ang-2 was found in GLUT-1, a known hypoxia-induced factor. Conclusion: The present study suggests that hypoxia may play an important role in inducing the expression of Ang-2 in CRC.