Abstract: To investigate the expression of endostatin, vascular endothelial growth factor C ( VEGF-C ), and vascular endothelial growth receptor 3 ( VEGFR-3 ) in non-small lung cancer ( NSCLC ) and lymph node tissues, and to explore their clinical significance. Methods: The immunohistochemical streptavidin-perosidase method was used to detect the expression of endostatin, VEGF-C, and VEGFR-3 in 98 cases of NSCLC after radical surgery. Results: The positive expression rates of endostatin, VEGF-C, and VEGFR-3 were 30.6%, 79.6%, and 61.2%, respectively. Endostatin and VEGF-C expression has significant correlation ( P = 0.025 ), whereas VEGF-C and VEGFR-3 expression also had significant correlation ( P = 0.007 ). Endostatin and VEGF-C expression in patients with different number of lymph node metastasis and N staging were significantly different ( P < 0.05 ). VEGFR-3 expression was correlated with differentiation ( P = 0.013 ), whereas VEGF-C expression was correlated with vascular thrombosis ( P = 0.050 ). The positive expression rates of endostatin and VEGF-C were 88% in positive lymph nodes, compared with the rates in negative lymph nodes which were 32.7% and 57.1% ( P < 0.001 ). More micro-lymphatic vessels were observed in the metastatic lymph nodes than in non-metastatic nodes. Conclusion: The expressions of endostatin and VEGF-C are related to lymphatic metastasis. Endostatin could decrease VEGF-C expression to inhibit lymphatic metastasis, and VEGF-C/VEGFR-3 could increase MLVD to help lymphatic metastasis, which is helpful for NSCLC therapy.