Peripheral sensory nerve abnormalities were investigated in long-term streptozotocin diabetic rats using quantitative analysis. To determine whether the characteristic structural changes occur with a proximodistal gradient, three levels of the sensory peripheral nervous system were investigated: the postganglionic segment of the dorsal root, the midportion of the sciatic nerve, and the distal sural nerve. Reduction of myelinated fiber size due to reduced axonal caliber was the most characteristic change at both proximal and distal levels of the peripheral nerve. The relationship between axonal size and myelin spiral length indicated a more severe axonal atrophy in the distal portion. The axonal atrophy was related to a proportional loss of axonal neurofilaments at proximal levels, whereas in the distal sural nerve the loss of neurofilaments exceeded that which would be expected for axonal size. The universal reduction of axonal size in diabetic nerve may be accounted for by impaired supply of neurofilaments or reduced neurofilament synthesis. Such cytoskeletal defects may, in turn, lead to distal axonal degeneration or contribute to the susceptibility of diabetic nerve to various external noxi, including ischemia and hypoglycemia.