Endothelial dysfunction of the optic microcirculation is considered to be the main pathogenetic mechanism in nonarteritic ischemic optic neuropathy. The aim of the present work was to assess whether a clinical improvement is correlated with a reduction in the endothelial activation markers by means of LDL apheresis (LDLA). Three weekly sessions of LDLA were administered in 23 patients affected by nonarteritic ischemic optic neuropathy. Statistically significant reductions were achieved in all parameters: total cholesterol (44.6%), LDL cholesterol (54.6%), fibrinogen (60.9%), von Willebrand factor (38.6%), sE-Selectin (22.6%), sICAM-1 (14%) and sVCAM-1 (15.5%), each of which was correlated with an improvement in the mean deviation of the visual field, although statistical significance for the single parameters was not reached. However, analysis of variance between the mean deviation improvement and the set of parameters taken together yielded highly significant results (p < 0.0001). LDLA was effective in reducing the values of all evaluated endothelial activation markers, and this trend was correlated with an improvement in the visual field.