BACKGROUND/AIMS: The inducible enzyme cyclo-oxygense-2 (COX-2) and its metabolic products are important mediators for angiogenesis. We investigated the expression of COX-2 and its downstream enzymes microsomal prostaglandin-E synthase (mPGES)-1, cytosolic PGES (cPGES) and thromboxane synthase (TXS), and correlated it with vascular endothelial growth factor (VEGF) expression and level of vascularisation in proliferative diabetic retinopathy (PDR) epiretinal membranes. METHODS: Membranes from five patients with active PDR and nine patients with inactive PDR were studied by immunohistochemistry. RESULTS: Vascular endothelial cells expressed COX-2, mPGES-1 and VEGF in 11, nine and six membranes, respectively. TXS was expressed in stromal cells in 12 membranes. There was no immunoreactivity for cPGES. There were significant correlations between number of blood vessels expressing CD34 and number of blood vessels expressing COX-2 (r(s) = 0.858; p<0.001), mPGES-1 (r(s) = 0.743; p = 0.002) and VEGF (r(s) = 0.845; p = 0.001) and number of cells expressing TXS (r(s) = 0.74; p = 0.002). The number of blood vessels expressing CD34 (p = 0.007), COX-2 (p = 0.027) and VEGF (p = 0.008) and stromal cells expressing mPGES-1 (p = 0.003), TXS (p = 0.04) and VEGF (p = 0.017) were significantly higher in active membranes than in inactive membranes. CONCLUSION: COX-2 and its metabolic products might contribute to PDR angiogenesis.