Abstract: We compared qualitative and quantitatively the neuroprotective effects of ketamine, nimodipine and lamotrigine in rat retinas submitted to acute ischemia and ischemia followed by reperfusion. Ischemia was induced by increasing of intraocular pressure above systolic blood pressure for 60 min. In reperfusion, intraocular pressure was reduced to normal levels for 45 min. Histological evaluation was performed by computer-assisted measurements from histologic sections. Ischemic retinas revealed a decrease in cells densities, cytoplasm vacuolization, pyknotic nuclei, edema and cell disorganization, when compared to contralateral-control eyes. Further, ischemia/reperfusion showed more evident retinal damage when compared to ischemic retinas. Lamotrigine pretreatment (25 mg kg-1) protected neurons mainly in ganglinar cell layer. Nimodipine pretreatment (20 μg kg-1) protected neurons of ganglion cell layer in ischemia and in ischemia/reperfusion the inner nuclear layer. Ketamine pretreatment (20 mg kg-1) protected neurons mainly in outer nuclear layer and inner nuclear layer in ischemia and ischemia/reperfusion. Present results suggest that lamotrigine, nimodipine and ketamine have potential neuroprotective properties in acute ischemia and ischemia/reperfusion models and all of them may have therapeutic implications for retina.