Objective To investigate the role of vascular endothelial growth factor D (VEGF-D) and vascular endothelial growth factor receptor 3 (VEGFR-3) in lymphangiogenesis and lymphatic metastasis of colon carcinoma by observing the expression of VEGFD and VEGFR-3, and calculated lymphatic vessel density (LMVD) in colon carcinoma. Methods The expressions of VEGF-D and VEGFR-3 were observed by SP immunohistochemistry in 55 colon carcinoma samples of different stages and differentiation degrees. LMVD in colon carcinoma was calculated by using Podoplanin as the specific marker of lymphatic endothelium. Results The positive expression of VEGF-D in colon carcinoma (54.5%) was higher than that in peritumoral tissues (P<0.05), and the expression rate of VEGFR-3 (69.1%) was higher than that in peritumoral tissues (P<0.01). The obvious correlation can be seen between the expressions of VEGF-D and VEGFR-3 (P<0.01) in colon carcinoma. We found that LMVD in carcinoma was higher than that in peritumoral tissues and the expression of VEGF-D in the groups with lymph nodes metastasis and invaded muscular layer and in phases Duke’s C and D was higher than that in the groups without lymph nodes metastasis, and noninvaded muscular layer and in phases Duke’s A and B (P<0.05). The correlation can be seen obviously between LMVD and the expression of VEGF-D(P<0.01). Conclusion The positive expression of VEGF-D in colon carcinoma is related with the tumor progression. It seems that VEGF-D induces lymphangiogenesis through its receptor VEGFR-3. VEGF-D and VEGFR-3 might play an important role in colon carcin