Oral lichen planus (OLP) is a chronic inflammatory disease of unknown cause, which possesses the potential for malignant transformation. Cyclooxygenases (COX) 1 and 2 are two enzymes known to convert arachidonic acid into prostaglandins. Recent studies have shown an overexpression of COX-2 in oral squamous cell carcinoma and its precursor lesions. The present study investigated the expression of the COX-2 protein in OLP by Western blot analysis. Thirty patients with different degrees of histologically confirmed disease activity participated in the study: 9 patients had a recent onset of active OLP, 12 patients had atrophic OLP with moderate or low activity, and 9 patients presented with atrophic OLP with complete loss of activity. The results showed a high expression of COX-2 in all OLP patients in comparison with the control group. The differences in COX-2 expression in the various stages of OLP were not statistically significant. In conclusion, our results suggest that COX-2 is present during the various clinical forms of OLP. The resulting sustained overexpression of COX-2 in the late stage of the disease could play a role in the malignant transformation of some OLP.