PURPOSE: To investigate the effect of brimonidine on the retinal ganglion cell survival in an optic nerve crush model. DESIGN: Experimental animal study. METHODS: Twenty-four Sprague-Dawley rats were divided into a study group of eight animals receiving intraperitoneal injections of brimonidine (I mg/kg) and into a control group of 12 animals receiving intraperitoneal saline injections. All injections were performed one hour before the optic nerve crash and daily afterwards. For each animal, the right optic nerve was crushed for 60 seconds by a microclip with 40-g power. At 23 days after the optic nerve crush, the retinal ganglion cells were retrogradely labeled by injecting 3% fluorogold into both sides of the superior colliculus of the brain. At four weeks after the optic nerve crush, the animals were sacrificed. Photographs taken from retinal flat mounts were assessed for number and density of the retinal ganglion-cells. RESULTS: The retinal ganglion cell density of the right eyes with an optic nerve lesion was statistically significantly (P = .02) higher in the brimonidine study group (1281 +/- 189 cells/mm(2)) than in the control group (1060 +/- 148 cells/mm(2)). Correspondingly, the survival rate (ratio of retinal ganglion cell density in the right eye divided by cell density in the left eye) was statistically significantly (P = .027) higher in the study group than in the control group (61.0% +/- 6.0% vs 53.5 +/- 8.0%). CONCLUSION: Intraperitoneal injections of brimonidine given prophylactically prior to and posttreatment daily after an experimental and standardized optic nerve crush in rats were associated with a higher survival rate of retinal ganglion cells. (Am J Ophthalmol 2009;147:326-331. (C) 2009 by Elsevier Inc. All rights reserved.)