PURPOSE. To investigate the effect of antithrombin III (AT III) on retinal ischemia/reperfusion (I/R) injury in rats. METHODS. The study was carried out on 10 Wistar albino rats (20 eyes) and four-vessel occlusion method was employed to induce retinal ischemia in this study. Rats were divided into two groups: Group I (control group, 10 eyes) and Group II (AT III, 10 eyes). In both groups, vertebral arteries were occluded bilaterally an electric needle coagulator under an operating microscope. A total of 48 hours after the initial procedure, the rats were re-anesthetized and both common carotid arteries were clamped to interrupt blood flow. In Group II, rats were injected intravenously with 250 U/kg of AT III 5 minutes before the induction of ischemia. Duration of ischemia was 30 minutes. At the end of this period, clamp was removed for the reperfusion of the eye for 4 hours. Following the reperfusion period, the animals were killed by decapitation. Retinal sections were evaluated under light and electron microscope. The signs of I/R injury at the microscopic level, i.e., cellular degeneration, vacuolization between retinal layers, increase in the retinal thickness due to edema, mononuclear cell infiltration, and apoptotic cells, were recorded for each group. RESULTS. Retinal sections obtained from the rats in the AT III group revealed a well preserved retinal structure. When average thickness values of the two groups were compared to each other, the difference was significant with respect to inner nuclear and inner plexiform layers indicating increased retinal thickness values in Group I due to tissue edema resulting from I/R injury. Similarly, mononuclear cell infiltration and apoptotic cell counts were found to be significantly higher in control group compared to AT III group showing the inhibitory effect of AT III on leukocyte infiltration and apoptotic cell death in rat retina. CONCLUSIONS. Antithrombin III attenuated I/R injury in rat retina. © Wichtig Editore, 2005.