Diabetes Mellitus (DM) is considered the major origin of diabetic neuropathy (DN). The latter is a major chronic diabetes complication characterized by functional and structural alterations in peripheral nerves. Thus, in the present study, we investigated the probable histological side effects of DM on the sciatic nerve and spinal cord in streptozotocin (STZ)- diabetic rats. This work included 20 female Wistar rats that were kept in regular conditions in their housing, and then they were divided into two main groups; control and diabetic groups (10 animals each).  Histological investigation of the sciatic nerve and spinal cord was performed by light microscopy (LM) and transmission electron microscopy (TEM). Moreover, S100 and GFAP Immunohistochemical expression were analyzed. DN group showed altered histological and ultrastructural features of the sciatic nerve and spinal cord in comparison to the control one. In addition, a notable reduction in S100 and GFAP immunostaining expression in the spinal cord of diabetic rats. The decline of the staining affinity was observed in the S100 stain of the sciatic nerve of diabetic rats.