Objective: To investigate the relations of vascular endothelial growth factor C (VEGF-C) expression and micro-lymphatic vessel density (MLVD) in cholangiocarcinoma tissues with the clinicopathologic features and prognosis of cholangiocarcinoma. Methods: The VEGF-C expression and D2-40 positive MLVD in 47 cases of cholangiocarcinoma tissues, 40 cases of adjacent non-tumor biliary tissues and 15 cases of normal biliary tissues were detected by immunohistochemical staining. The correlation between VEGF-C and their relations with clinicopathological characteristics and prognosis were analyzed. Results: The positive expression rate of VEGF-C in cholangiocarcinoma tissues was significantly higher than those in adjacent non-tumor and normal biliary tissues (both P<0.05), and the MLVD in both cholangiocarcinoma and adjacent non-tumor biliary tissues were significantly higher than that in normal biliary tissues (both P<0.05). The VEGF-C expression and MLVD were closely related to the depth of invasion, TNM stage and lymphatic metastasis of cholangiocarcinoma (all P<0.05), moreover, MLVD was also relevant to the differentiation degree of cholangiocarcinoma (P<0.05). MLVD in the VEGF-C positive cholangiocarcinoma tissues was significantly higher than that of the negative ones (P<0.05), and the VEGF-C expression was positively correlated with MLVD (r=0.615, P<0.05). The patients with negative VEGF-C expression had better prognosis than those with positive VEGF-C expression (P<0.05), and MLVD in the cholangiocarcinoma tissues of the recurrent cases was significantly higher than that of the non-recurrent ones (P<0.05); further, MLVD showed a negative correlation with the survival time of the patients (r=–0.542, P<0.05). Conclusion: VEGF-C expression and MLVD are closely related to the lymphatic metastasis and prognosis of cholangiocarcinoma. VEGF-C may potentially become one of the effective indicators for predicting lymphatic metastasis in patients with cholangiocarcinoma.