Parvalbumin (PA), one of the Ca2+-binding neuronal marker proteins, has been revealed to exist in the myelinated axons of the posterior root of the spinal cord and the peripheral nerve of rats. To investigate the role of PA for the genesis of diabetic neuropathy, the levels of PA in the sciatic nerve of normal and streptozotocin-induced diabetic rats were measured by radioimmunoassay (RIA) for PA. The immunohistochemical distribution of PA in the sciatic nerve from both groups was also studied. The RIA for PA revealed that the levels of PA in the sciatic nerve of diabetic rats were significantly decreased when compared with those of normal rats. However, the contents of S-100 protein, another type of Ca2+-binding glial marker protein, did not show any significant difference in the sciatic nerve from both groups. Immunohistochemically, the amount of PA containing myelinated axons of the diabetic nerve was markedly decreased when compared with nondiabetic subjects. These results suggest that the decreased level of PA in the peripheral nerve might contribute to the genesis of diabetic neuropathy.