Objective To investigate whether COX-2/PGE2 can regulate vascular endothelial growth factor (VEGF) expression through activating Wnt/β-catenin signal pathway in human colorectal cancer cells. Methods PGE2 and (or) COX-2 selective inhibitor NS-398 was used to treat LoVo cells for 24 h, and then COX-2 and β-catenin protein expression was detected by Western blotting analysis. PGE2 and (or) β-catenin/tcf selective inhibitor FH-535 were used to treat LoVo cells for 24 h, and then the levels of VEGF was determined by ELISA. Routinely cultured LoVo cells were taken as control. Results Compared with the control group, PGE2 not only increased COX-2 protein expression, but also increased the levels of β-catenin in the total cell, cytosolic and nuclear proteins (being 3.8 folds, 2.7 folds, and 3.0 folds of the control, respectively, P<0.01). COX-2 selective inhibitor not only decreased COX-2 protein expression, but also decreased the levels of β-catenin in the total cell, cytosolic and nuclear proteins (being 0.3 folds, 0.3 folds, and 0.2 folds of the control, P<0.01). Compared with the control group, PGE2 increased VEGF expression in LoVo cells (being 1.6 folds of the control, P<0.01), and β-catenin/tcf selective inhibitor decreased VEGF expression in LoVo cells (being 0.68 folds of the control, P<0.01). Co-treatment of LoVo cells with β-catenin/tcf selective inhibitor and PGE2 showed no great effect on VEGF expression. Conclusion COX-2/PGE2 can increase β-catenin protein level, subsequently activate Wnt/β-catenin signal pathway and promote VEGF expression,which might be one of the mechanisms for COX-2/PGE2-induced angiogenesis in colon cancer.