Squamous cell carcinomas of the head and neck are characterized by their high tendency for invasion and metastasis. Several studies have identified the roles of matrix metalloproteinases (MMPs), vascular endothelial growth factors (VEGF) and urokinase plasminogen activators (uPA) in this process. Photodynamic Therapy (PDT) is an emerging treatment currently in clinical practice for the treatment of early cancer. Here we evaluate, in vitro, the influence of PDT on the expression of these molecules. A series of human keratinocyte cell lines derived from human oral squamous cell carcinomas (OSCC) were used as the PDT 'targets' in this study. Each cell line was subjected to sublethal dose of PDT. Activity of MMP-2, MMP-9, MMP-13, uPA and VEGF were evaluated at protein levels using zymography and ELISA on culture medium. For uPA, a chromogenic assay was performed. Gelatin zymography results revealed that, in control medium, MMP-9 and MMP-2 were secreted in proform. MMP-2 was highly expressed by H376 cells while VB6 and UP cells relatively show similar MMP-2 with comparatively low expression. For MMP-9, the latent type was highly expressed by VB6 cells and only slightly by H376, while active-MMP-9 was expressed by VB6 cell line only. Following PDT, both active and latent MMP-2 and MMP-9 were down regulated by UP and VB6 cells (p<0.001), while H376 showed an increase in active-MMP-2. These observations were supported by ELISA. This study has demonstrated that, PDT causes the suppression of factors responsible for tumour invasion which may be of therapeutic value.