The incidence of gastric cancer worldwide, and in particular in developing countries, has shown a markedincrease. Poor prognosis of gastric cancer patients occurs due to the rapid metastasis of the disease via thelymphatic and blood vessels. The aim of this study was to investigate the expression and the clinical significanceof D2-40 and CD34 in human gastric cancer. D2-40 and CD34 expression wasdetected in 1,072 cases of Chinesepatients with gastric carcinoma using immunohistochemistry. The lymphatic vessel density (LVD) and microvesseldensity (MVD) were calculated and analyzed and the correlation with the clinicopathological factors and prognosiswas determined. The LVD and MVD of the gastric cancer cases were significantly higher compared to those ofnormal tissues (P < 0.05). The expression of D2-40-LVD and CD34-MVD in the malignancies were positivelyrelated to the age, tumor size, invasion depth, lymphatic metastasis and pathological tumor-node-metastasis(pTNM) (P < 0.05); However, no statistically significant difference was identified between them with the patientgender (P > 0.05). Up-regulation of D2-40 and CD34 expression was significantly correlated with the poor survivalrate in univariate and multivariate analyses. The LVD marked by D2-40 and the MVD marked by CD34 werepositively correlated to the clinicopathological factors of the malignancies and may play important role in thedevelopment and progression of gastric cancer.