Objective: To investigate the expression of angiopoietin-2 (Ang-2) and vascular endothelialcell growth factor (VEGF) in oral squamous cell carcinoma (OSCC) and their correlations with clinicopathologic parameters, angiogenesis and vessel maturation of OSCC. Methods: The expression of Ang-2 and VEGF was detected in 41 speciments of human OSCC, 30 adjacent noncancerous oral tissues and 10 specimens of normal oral mucosa by conventional immumohistochemistry. Microvessel density (MVD) and vessel maturation index (VMI) were also assessed by double-labelling immumohistochemistry staining against CD34, a marker of pan-endothelial cells, and that against alpha-smooth muscle actin (α-SMA), a marker of mural cells (pericytes/smooth muscle cells). Results: The positive expression rate of Ang-2 and VEGF in 41 OSCC tissues was 51.22% and 63.42%, respectively. The expression of Ang-2 and VEGF was significantly higher in OSCC than in adjacent noncancerous oral tissues (all P<0.05) and normal oral mucosa (all P<0.05). In the clinicopathologic parameters, the Ang-2 expression was closely correlated with tumor lymph node metastasis (P<0.01) and the VEGF expression was correlated with tumor differentiated degree (P<0.05), but there was no significant correlation among the Ang-2 and VEGF expression and patients' sex, age and TNM stages (all P>0.05). The MVD of OSCC positive for both Ang-2 and VEGF was significantly higher than that of OSCC negative for both Ang-2 and VEGF (P<0.05). The VMI of OSCC positive for Ang-2 was significantly lower than that of OSCC negative for Ang-2 (P<0.05). When Ang-2 expression was combined with the staus of VEGF expression, MVD of OSCC positive for both Ang-2 and VEGF was the highest (51.08±2.99) as compared with that of other status in patient with OSCC (all P<0.05). Conclusion: The overexpression of Ang-2 and VEGF may play a crucial role in the development of OSCC. They are closely associated with angiogenesis and vessel maturation of tumor. © Springer-Verlag Berlin Heidelberg 2005.