The objective of this study was to investigate the roles of matrix metalloproteinases (MMP-2, MMP-9) and cyclooxygenase-2 (COX-2) in the pathogenesis of vocal fold polyps (VFPs). In this study, 20 VFPs and 8 normal vocal fold (VF) specimens were obtained from subjects undergoing surgery. Staining intensities were semiquantitatively assessed and statistically analyzed. Significant increases were observed in the expressions of MMP-2, MMP-9, and COX-2 in stromal spindle cells (P=0.00) and vascular wall (P=0.04, P=0.00, P=0.00) of VFPs compared with normal VFs. MMP-2 expression in surface epithelium basal cells (P=0.00) of VFPs showed enhancement compared with normal vocal folds, whereas MMP-9 and COX-2 expressions showed no significant differences. Our study showed that gelatinases and COX-2 may play a role in the development of VFPs. This is the first study to document the expression of gelatinases and COX-2 in VFPs.