In this study, neurological complications associated with spontaneously occurring feline diabetes were comprehensively evaluated. Physical and neurological examinations, electrophysiological assessment, and biochemical and histological analysis of nerve and muscle biopsy specimens were performed in 19 diabetic cats and referenced to similar data from 28 nondiabetic cats without evidence of neuropathy. Compared to nondiabetic cats, diabetic cats exhibited a range of functional, structural, and biochemical defects that, depending on severity, manifested as striking neurological dysfunction. A broad spectrum of clinical signs was apparent with the most notable and severe impairment being a plantigrade posture when standing or walking. A sensorimotor neuropathy, characterized by conduction deficits and increased F wave and cord dorsum potential latencies, was present in both pelvic and thoracic limbs and, except in the most severely affected animals, occurred with little or no electromyographic abnormality. As for nerve structural abnormalities, Schwann cell injury was prevalent and included myelin defects, such as splitting and ballooning, and demyelination, although axonal degeneration was noted in biopsies from severely affected cats. Evidence of polyol pathway activity consisted of marked increases in nerve fructose without appreciable sorbitol accumulation. The occurrence of diabetic neuropathy in the cat, a relatively large animal with a long life span and long nerves, provides unique opportunities to study the development and treatment of this debilitating complication.