The inducible enzyme cyclooxygenase-2 (COX-2) is an important mediator of angiogenesis and tumor growth. Several reports have indicated that vascular endothelial growth factor (VEGF)-positive tumors are associated with an increased amount of COX-2 protein. This study evaluated the significance of COX-2 in 34 patients with endometrial carcinoma and its relationship to angiogenesis. Immunohistochemical expression of COX-2 and VEGF was analyzed on paraffin-embedded tissue sections. Microvessel density (MVD) of endometrial carcinoma was also determined with anti-CD(34) as the label. COX-2 messenger RNA (mRNA) was analyzed by reverse transcription-polymerase chain reaction. The expression rate of COX-2 in 34 cases was 64.7% but not in control endometrium. COX-2 mRNA was higher in tumor specimens than in normal tissues. The level of COX-2 expression was higher in grade 2 tumors than in grade 3 tumors (P < 0.05). MVD was higher in COX-2-positive and VEGF-positive cases than in COX-2-negative and VEGF-negative cases (P < 0.05). The expression of COX-2 was positively correlated with the expression of VEGF and MVD (P < 0.05 and P < 0.01, respectively). The present findings suggest that overexpression of COX-2 may induce the expression of VEGF, increase angiogenesis, and enhance tumor growth.