No specific therapy is available for non-arteritic ischemic optic neuropathy (NAION), a blinding disease, which is related to microvascular insufficiency of the optic disc and white matter lesions in brain MRI representing ischemia. We hypothesize that pentoxifylline, traditionally used for treatment of peripheral vascular disease due to its ability to decrease viscosity and increase erythrocyte flexibility, may be useful to improve blood flow in patients with NAION. Positron emission tomography (PET) to determine the change in glucose metabolic rate in the visual cortex of patients with NAION versus age-matched controls was performed after 3 months' administration of pentoxifylline. Eight patients clinically diagnosed with NAION underwent clinical and laboratory evaluation, brain MRI and PET with fluoride-18 fluorodeoxyglucose (FDG). All patients were treated with oral pentoxifylline 400 mg three times a day for a period of at least 3 months. Three patients were included in the final PET data analysis. At baseline, PET revealed bilateral metabolic decreases especially in the ventral visual stream in all patients compared with 56 age- and gender-normalized controls. Metabolic changes were seen in the dorsal stream areas 17, 18, and 19, cerebellar region, dorsolateral prefrontal cortex, medial temporal lobe, and frontal eye fields 8 and 6. At 3 months following pentoxifylline, all three patients included in the final PET data analysis showed partial normalization from the baseline metabolism. Metabolic imaging with FDG-PET in NAION provides functional information not attainable with conventional brain MRI. The exact relevance of these results, and the role of pentoxifylline in these metabolic changes, should be determined by means of a larger randomized and controlled trial.