Brimonidine, a selective alpha(2)-adrenoceptor agonist, has recently been shown to be neuroprotective as it significantly improves survival of retinal ganglion cells (RGCs) after calibrated optic nerve injury in rats. In the present study, we examined the effect of brimonidine (alpha(2)-adrenoceptor agonist) on RGC survival after increased intraocular pressure (IOP) in adult rats. RGCs were prelabeled by bilateral tectal injection of 5% Fluoro-Gold (FG). Two days later, unilaterally IOP was increased 2.2-2.5 times (28-30.5 mmHg) that of the normal pressure (12.5-14.5 mmHg) by cauterization of three episcleral veins. The elevated IOP was maintained throughout the duration of the experiment. Rats were treated intraperitoneally with brimonidine (1 mg/kg) or phosphate-buffered saline (PBS) once per week beginning either before (group A) or after (group B) increasing the IOP. Another group of rats was left as the control with elevated IOP but without any brimonidine/PBS treatment. Rats were euthanized at 3, 4 and 5 weeks after IOP elevation. Identifiable RGCs were counted and compared between control and experimental groups. Brimonidine significantly protected RGCs from elevated IOP-induced cell death. In control rats with three-vein cauterization, there was 5-6% cell death per week. Almost all RGCs were protected following brimonidine treatment for 3 weeks both in groups A and B. At 4 weeks, there was 4.5% cell death in group A and 6.5% in group B. At 5 weeks, cell death was 5.9% in group A and 6.2% in group B. The difference in cell death in groups A and B was insignificant. No significant differences were observed between PBS-treated and control groups. No significant changes in elevated IOP was found after brimonidine or PBS treatment when compared with the nontreated control group. Although pressure remained elevated throughout the length of the experiment, 3 weeks later the amount of cell death gradually increased in brimonidine-treated animals.