ABSTRACT Objective: To explore the expression and clinical significance of interleukin-6 (IL-6), cyclooxygenase-2(COX-2) and vascular endothelial growth factor (VEGF) in cholangiocarcinoma. Methods: 80 patients with paraffin-embedded specimens of cholangiocarcinoma surgically resected and pathologically diagnosed were selected as cholangiocarcinoma group, and the normal bile duct tissues adjacent to cancer as control group. The expressions of IL-6, COX-2 and VEGF in the two groups were detected by immunohistochemical SP method and compared. The positive expressions of VEGF, COX-2 and IL-6 in cholangiocarcinoma tissues were analyzed and compared with clinical data. Spearman grade correlation was used to analyze the correlation of expression of VEGF, COX-2 and IL-6 in cholangiocarcinoma. Results: The positive expression rates of VEGF, COX-2 and IL-6 in cholangiocarcinoma group were significantly higher than those in control group, and there was significant difference between the two groups (P<0.05). The positive expression rates of VEGF, COX-2 and IL-6 in cholangiocarcinoma tissues were correlated with lymph node metastasis, TNM stage and differentiation degree (P<0.05), but not with sex, age and tumor diameter (P>0.05). The positive expression rates of VEGF, COX-2 and IL-6 in cholangiocarcinoma tissues were correlated with lymph node metastasis, TNM stage and differentiation degree(P<0.05). Spearman grade correlation analysis showed that there was a positive correlation between the positive expression rate of VEGF and COX-2, IL-6 in cholangiocarcinoma (P<0.05), and the positive expression rate of COX-2 and IL-6 in cholangiocarcinoma (P<0.05). Conclusion: The IL-6, COX-2 and VEGF are highly express in cholangiocarcinoma tissues, which are closely related to the growth and metastasis of cholangiocarcinoma. Detection of IL-6, COX-2 and VEGF is helpful in judging the progress of cholangiocarcinoma.