Epigallocatechin-3-gallate (EGCG) is a powerful antioxidant with suggested neuroprotective action. This study investigated the protective effects of EGCG against retinal ganglion cells (RGCs) degeneration in an animal model of glaucoma. C57BL/6J mice (n = 54) were divided randomly into four groups: normal control group (group A, n = 12); EGCG control group with EGCG in drinking water (group B, n = 12); microbeads control group with anterior chamber microbeads injection to induce elevation in intraocular pressure (IOP) plus normal drinking water (group C, n = 18); and EGCG study group receiving an anterior chamber microbeads injection plus EGCG in drinking water (group D, n = 12). Animals were treated orally with either vehicle or EGCG (50 mg/kg x d). IOP was measured and animals were sacrificed at days 15 and 27. Neurons were retrograde-labeled by fluorogold and immnunolabeled by class III beta-tubulin to quantify RGCs in the retinal ganglion cell layer on flat mounts histologically and compared. All mice that received microbeads injections (groups C and D) developed IOP elevation higher than un-injected control mice. At days 15 and 27, progressive loss of RGCs was observed after microbeads injection in group C (P < 0.01). In contrast, the fluorogold-labeled RGC density and class III beta-tubulin-positive RGC density were significantly higher in group D as compared to group C (P < 0.01) but significantly lower than group B (P < 0.01). These parameters did not differ significantly between groups A and B (P > 0.05). The findings suggest the consumption of EGCG plays a neuroprotective role on RGCs in a mouse model of elevated IOP. (C) 2015 Elsevier Ireland Ltd. All rights reserved.