Stroke is associated with high mortality and major disability burdens worldwide, but there are few effective and widely available therapies. Tau plays an important role in promoting microtubule assembly and stabilizing microtubule networks with phosphorylation regulating these functions. Based on the "ischemia-reperfusion theory" of Alzheimer's disease, some previous studies have focused on the relationship of tau and Alzheimer lesions in experimental brain ischemia. Thus, we hypothesize that the alterations in phosphorylation of tau are critical to microtubule dynamics and metabolism, and contribute to the pathophysiologic mechanisms during brain ischemia and/or reperfusion processes. We infer that regulation of phosphorylation of tau may be considered as a potential new therapeutic target in ischemic stroke.