Cyclin-dependent kinase 5 (cdk5) is a homologue of cell division cycle 2 (cdc2)-like protein kinase. It is mainly expressed in neurons, and supposed to be involved in the dynamic change of neurocytoskeleton structure seen in the brain after ischemia. In the present study, we investigated immunoreactivity for cdk5 and its critical regulatory subunit p35 in rat brain after 90 min of middle cerebral artery (MCA) occlusion. In the control brain, immunoreactive cdk5 was present in some neurons, while p35 was evident in almost all neurons. At 1 h after blood flow restoration, both of them were remarkably increased in the MCA territory. At 3 h, both immunoreactivities were decreased in the ischemic core region, while they became stronger in neurons at the boundary zone of the MCA territory, which decreased thereafter. These results might suggest that increased cdk5 activity in the brain after ischemia caused depolymerization of neurocytoskeletons, which resulted in neuronal cell death.