Purpose.This study examines the contribution of ocular and systemic factors to diabetic keratoepitheliopathy.Methods.The presence and severity of keratoepitheliopathy was investigated in 114 eyes of patients with diabetes and 59 eyes of patients without diabetes. The ocular factors examined were the status of the lipid layer of the tear fluid assessed with the specular reflection video-recording system, corneal sensitivity using the Cochet–Bonnet method, tear volume by the cotton thread test, tear film stability by tear breakup time, and grade of diabetic retinopathy. The systemic factors examined included patient age, hemoglobin A1c value, and duration of diabetes mellitus. Multivariate regression analysis was performed to assess the factors related to keratoepitheliopathy.Results.The incidence of keratoepitheliopathy was 22.8% and 8.5% in patients with and without diabetes, respectively. Ocular measures, such as nonuniformity of tear lipid layer, corneal sensitivity, and tear breakup time, were significantly worse in patients with diabetes than in patients without diabetes (p< 0.05). Multivariate regression analysis showed that the status of the tear lipid layer was significantly relevant to diabetic keratoepitheliopathy (p< 0.05).Conclusion.Qualitative abnormalities in tear secretion seem relevant to the development of diabetic keratoepitheliopathy. The tear lipid layer interference pattern may yield useful information for the elucidation of the mechanism and treatment of diabetic keratoepitheliopathy.