Symptomatic neuropathy is a common manifestation of diabetes mellitus, and sensory, motor, or autonomic symptoms occur in approximately 10% of all diabetic patients. Animal models may be useful to study the metabolic and electrophysioiogic abnormalities peculiar to diabetic neuropathy. Genetic animal models, including the Chinese hamster, ob/ob mouse, db/db mouse, BB-wistar rat, and SSDR rat or chemically induced or nutritional models of diabetes mellitus provide the potential to use animals to study human neuropathy; however, to date, few characteristics of human diabetic neuropathy have been clearly demonstrated in any of these animal models. Better characterization of the neuropathy of existing animal models with emphasis on evaluation over long periods of time is recommended. These studies should include a cross-disciplinary approach using biochemical, electrophysioiogic and morphologic techniques. Specific future approaches to study diabetic neuropathy using chemical models is outlined in this chapter.