Introduction: Vitiligo is an acquired depigmenting disordercharacterized by absence of melanocytes from vitiligo lesions.Cyclooxygenases (COXs) are key enzymes in the conversion ofarachidonic acid to prostaglandins. Cyclooxygenase-2 (COX-2)expression plays a major role in prostaglandin E2 (PGE2) production.PGE2 plays an important role in tyrosinase activation and melanocytesdendricity and melanogenesis.• Aim of the study: To determine the role of COX-2 and PGE2 in thepathogenesis of vitiligo.• Patients and methods: The study included 22 vitiligo patients and 20controls. One skin biopsy was obtained from the depigmented lesions,another one from the clinically normal skin in patients and one skinbiopsy from controls. Skin biopsies were examined for gene expressionof COX-2 by reverse transcription-polymerase chain reaction (RT-PCR)and PGE2 level by Enzyme-linked immunosorbent assay (ELISA). Bloodsamples were withdrawn from patients and controls to assess the plasmalevel of PGE2 and COX-2 using ELISA technique and COX-2 activity byCyclooxygenase Enzyme Immunometric Assay Kit.• Results: The expression of COX-2 mRNA was significantly higher inskin of controls than in lesional and non-lesional skin of patients(P<0.001) and the level of PGE2 was significantly higher in skin ofcontrols than in lesional and non-lesional skin of patients (P<0.001,P=0.003 respectively). The plasma level and activity of COX-2 and theplasma level of PGE2 were significantly higher in patients compared tocontrols (P < 0.001).• Conclusion: COX-2 and PGE2 could contribute to the development ofvitiligo through their immunomodulatory role or locally through theirrole in melanogenesis.