AIM: To investigate the expression of cyclooxygenase-2 (COX-2) and its correlation with the angiogenesis and clinicopathological features in esophageal carcinoma. METHODS: Ninety tumor specimens resected from patients with squamous cell carcinoma of the esophagus were obtained, and 34 corresponding paracancerous normal tissues were randomly selected as the controls. Immunohistochemical staining was used to detect the expression of COX-2. Monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was determined by counting the CD34-positive cells. The correlations of COX-2 expression with MVD and clinicopathological parameters of the patients were analyzed. RESULTS: The positive rates of COX-2 and MVD expression in the cancerous tissue were 84.4% and 29.68 ± 3.81, respectively, which were significantly higher than those in the normal esophageal mucosa (20.6%, χ2 = 45.47, P = 0.00; 15.12 ± 2.80, t = 20.28, P = 0.00). COX-2 expression was closely correlated with clinical TNM classification (χ2 = 7.99, P = 0.005), cellular differentiation (χ2 = 7.99, P = 0.005) and lymph node metastasis (χ2 = 9.61, P = 0.002) in squamous cell carcinoma of the esophagus. The mean values of MVD were associated with clinical TNM classification (t = -7.09, P = 0.00) and lymph node metastasis (t = -7.90, P = 0.00). The spearman rank correlation test showed that tumor MVD was positively associated with COX-2 expression (r = 0.607, P = 0.00). CONCLUSION: Over-expression of COX-2 is correlated with tumor invasion and lymph node metastasis in esophageal carcinoma, suggesting that COX-2 contributes to the development of esophageal cancer by promoting angiogenesis.