Objective: To study the expression and the significance of Angiopoietin-1 (Ang-1) through observing the correlations among the expression of Ang-1 to clinicopathologic characteristics and microvessel density (MVD) in oral squamous cell carcinoma (OSCC). Methods: Expressions of Angiopoietin-1 and CD34 in 41 human OSCC tissues, 30 adjacent noncancerous oral tissues and 10 normal oral mucosas were detected by immunohistochemical SABC method. MCD was also assessed. Results: Of the 41 OSCC tissues, 41.46% (17/41) was Ang-1 positive. The expression of Ang-1 was significantly lower in OSCC than that in adjacent noncancerous oral tissues (P＜0.05) and normal oral mucosa (P＜0.05). The Ang-1 expression was significantly higher in high differentiated tumor than that in moderately differentiated tumor (P＜0.05). The MVD was significantly higher in Ang-1-negative OSCC than in Ang-1-positive OSCC (P＜0.01), and negatively correlated with the expression of Ang-1 (r=-0.32, P＜0.05). Conclusion: Down-regulated expression of Ang-1 may play a crucial role in the development of OSCC. It negatively regulated the angiogenesis of tumor.