Hyperglycemia plays a critical role in the development and progression of diabetic encephalopathy. A few studies have focused on a disintegrin and metalloprotease with thrombospondin type I repeats-13 (ADAMTS-13) expression in the central nervous system (CNS), and its function continues to remain unclear. The purpose of this study was to compare the expression of ADAMTS-13, neuron specific enolase (NSE), neurofilament (NF), neuronal nitric oxide synthase (nNOS) and glial fibrillary acidic protein (GFAP) in brain tissues of experimental streptozotocin (STZ)-induced diabetic rats. Expression of ADAMTS-13 (P < 0.001), nNOS (P < 0.001), NSE (P < 0.001) and NF (P < 0.001) expressions in the brain tissue markedly increased while GFAP decreased (P < 0.001) in diabetic animals versus controls. The most prominent finding of our study was that ADAMTS-13 expression increased significantly, suggesting that it may play an important function/s in the regulation and protection of the blood-brain barrier integrity and central nervous system microenvironment in diabetes. The results also suggested that nitric oxide production may increase due to increased nNOS expression and this also might contribute to neuropathology related with diabetes. Furthermore, increased expression of ADAMTS-13, NSE, NF and decreased expression of GFAP may give an idea of the disease progress and thus may have a critical diagnostic significance. To the best of the authors' knowledge, this is the first report on ADAMTS-13 expression in the CNS of STZ-induced diabetic animals.