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AIM: To explore the expression and clinicopathological significance of cyclooxygenase-2 (COX-2) and microvessel density (MVD) in gastric carcinogenesis,and to investigate their roles in the invasion and the relationship between biological behaviors and prognosis of gastric cancer.METHODS: Using Envision immunohistochemistry,COX-2 and CD34 expressions in gastric cancer tissue array were examined. MVD was counted and the relationship between the biological behaviors and prognosis was analyzed.RESULTS: The expression of COX-2 in gastric cancer tissue was significantly higher than that in normal mucosa (x2 = 12.191, P ＜ 0.05). The over-expression of COX-2 in gastric cancer was obviously related to metastasis and depth of invasion (x2= 6.315, P ＜ 0.05),but not related to the histological type and Borrmann type (x2 = 5.391 and x2 = 2.228, respectively). Moreover,MVD in gastric cancer tissues was significantly higher than that in the normal mucosa (65.49 ± 20.64 vs 36.21± 18.47, t/F = 7.53, P ＜ 0. 05). MVD was related to the histologic type and metastasis (t/F = 3.68 and t/F = 4.214, respectively, P ＜ 0. 05), but not related to the depth of invasion and Borrmann type (t/F = 0.583 and t/F = 0.459, respectively). MVD in COX-2-positive tissues was markedly higher compared to COX-2-negative tissues, indicating a positive correlation between COX-2 expression and MVD (t = 13.12, P ＜ 0.05).CONCLUSION: Tissue microarray (TMA) is a powerful tool for rapid identification of the molecular alterations in gastric cancer. COX-2 expression, via inducing angiogenesis, may play an important role in gastric carcinogenesis. It could be served as a determinant factor for clinical prognosis and curative effect.