OBJECTIVE To investigate N-methyl-D-aspartate (NMDA)-induced morphological changes in the retina in rats. METHODS Thirty-two healthy Sprague-Dawley (SD) rats were randomly divided into 4 groups. Eight rats were in normal control group. The rest 24 rats were equally distributed into 3 experimental groups to receive a single dose of 2 microL intravitreal injection of 3 different concentrations of NMDA (namely 10 nmol, 20 nmol, and 40 nmol per injection ) into the right eyes. The left eyes received 2 microl 0.1 mol PBS used as a self-control. Seven days after the NMDA injection, all rats were killed and the eyes were enucleated. The extent of NMDA-induced neurotoxicity in the retina was quantified by the thickness of the inner plexiform layer (IPL) of the retina at 1.0 - 1.5 mm from the margin of the optic disc of 6 rats in each group. The retinas and optic nerves from the other 2 rats were processed for histopathologic investigation under electronic microscope and light microscope. RESULTS The thickness of IPL was decreased. There was significant difference between any of the above 2 groups (All P < 0.05). The higher the concentration of NMDA solution, the more decreased thickness of the IPL. No obvious abnormality was observed in the outer layer of the retina. There was degeneration of the optic nerve axons in the NMDA-treated eyes of the experimental groups. The extent of morphological changes of the axons of the optic nerve was related to the dose of NMDA administrated. Ultra-structural study also showed some characteristic changes of apoptosis such as shrunken nucleus and clumping of chromatin at the nuclear membrane in retinal ganglion cell lay (RGCL) and inner nuclear layer (INL). CONCLUSION Administration of NMDA can result in the thinning of IPL and the dose-dependent degeneration of the optic nerve. Apoptosis may be the main morphological evidence of NMDA receptor-mediated cell death in RGCL and INL in adult rat retinas. NMDA-induced damage is similar to glaucomatous degeneration to some extent.