Neurodegenerative tauopathy characterized by hyperphosphorylation tau has been implicated in the pathophysiology of diabetic central nervous system (CNS) complication. Emerging evidence has suggested that hyperphosphorylation tau is caused by an imbalance of protein kinase and phosphatase activity. This review focuses on the contributions of impaired insulin signaling to diabetes-related tauopathy through disrupting the balance of tau-related protein kinases and phosphatases. In addition, we describe tau pathology as a potential target for central neuronal degeneration in diabetes mellitus.