Pur po se: The aim of our study was to investigate the neuroprotective effects of topical α-tocopherol in optic nerve crush model of rat and to compare its efficacy with that of systemic α -tocopherol. Ma te ri al and Met hod: 50 eyes of 25 Wistar albino rats were included. The eyes were divided into six groups. Optic nerve crush was performed in Groups 1, 3, 5. Additionally, systemic and topical α-tocopherol therapies were given to Groups 1 and 3, respectively. No treatment was applied in Group 5. Groups 2, 4, and 6 were the fellow eyes of the animals comprising Groups 1, 3, and 5. Eyes were enucleated at day 45 of the study. Retinal ganglion cells (RGCs) were counted with light microscopy. Re sults: Mean RGC numbers were 14.5±3.7 (10.3-20) and 27.5±2.6 (24-30) in Groups 5 and 6, respectively (p: 0.001) They were measured to be 26.6±7.8 (19-45) and 24.6±3.9 (20-32) in Groups 1 and 2 and 21.1±7.1 (11-34) and 27±7.5 (18-42) in Groups 3 and 4 (p:0.659, p:0.094, respectively). There was no difference in Groups 2 and 4 compared with Group 6 (p:0.210, p:0.299, respectively). Dis cus si on: Topical α-tocopherol has a significant neuroprotective effects in optic nerve crush model of rat and may be used in the future for the treatment of optic neuropathies such as glaucoma. (Turk J Ophthalmol 2013; 43: 161-6)