Background: Breakdown of extracellular matrix (ECM) is one of the important hallmarks of cancer progression which facilitates the invasion of tumoral cells to the surrounding tissue. Matrix metalloproteinases (MMPs) can degrade various components of the ECM and basement membrane. The aim of this study was to determine the role of matrix metalloproteinases-9 protein in the biologic behavior of oral squamous cell carcinoma (OSCC) and its relation with tumor angiogenesis. Material and Methods: In this study 42 OSCC and 15 normal epithelium were reviewed by immunohistochemical staining for matrix metalloproteinases-9 and CD105. Results: Matrix metalloproteinases-9 expression was detected in 32 OSCC specimens (76.1%), with 28 specimens (66.6%) showing moderate or strong expression. We observed that the expression level of matrix metalloproteinases-9 was positively correlated with the status of lymph node metastasis (N0vs. N1) ( P =0.00), and clinical stage (I-II vs. III-IV) in OSCC patients. Microvessel density in intratumoral tissue has an association with lymph node metastasis and advanced clinical stage ( P =0.003 and p =0.01, respectively). We observed that tumors with matrix metalloproteinases-9 overexpression had a higher microvessel density counts compared with tumors with absent or focal immunostaining (16.2±5.6 vs 10.3±3.5 respectively, P =0.03). Conclusions: In conclusion present results demonstrate the marked expression of matrix metalloproteinases-9 and CD105 in OSCC and suggest that the expression of these markers is associated with tumor progression and could offer additional information about the aggressiveness of OSCC. In addition a significant relationship was noted between microvessel density count and expression of matrix metalloproteinases-9 which suggest that MMP9 expression may be closely related to tumor angiogenesis