OBJECTIVES: The aim of this study was to investigate the effect of corticosteroid treatment on topical and systemic metalloproteinase levels of patients with nasal polyposis (NP). STUDY DESIGN: Prospective clinical trial. METHODS: The study included patients undergoing a paranasal sinus operation due to NP. Oral corticosteroid therapy was performed on all patients before endoscopic sinus surgery. Endoscopic and radiological evaluation were performed and nasal tissue specimens and venous blood samples were collected before (preop phase) and after corticosteroid treatment (periop phase) and also one month after surgery (postop phase). Endoscopic and computed tomography scan findings were scored adequately and all tissue and blood samples were examined cumulatively. RESULTS: The study included 27 patients with inflammatory NP. Preop tissue matrix metalloproteinase-2 (MMP-2) levels were found to be significantly lower than preop and postop concentrations. In contrast, periop serum MMP-2 levels were found to be significantly higher than preop and postop concentrations. Periop tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were also found to be significantly lower than preop and postop concentrations, similar to MMP-2 tissue concentrations. However, there was no statistical difference among tissue MMP-9 concentrations of the three phases. In addition, there was also no statistical difference among serum MMP-9 levels of the three phases. CONCLUSIONS: Oral corticosteroid treatment especially reduces tissue MMP-2, then TIMP-1. Severity of nasal polyposis primarily correlates with increasing tissue MMP-2/TIMP-1 ratio, then MMP-9/TIMP-1. These results suggest that selective inhibition for MMP-2 and activation for TIMP-1 might be a novel therapeutic strategy for patients with nasal polyposis.