Expression of midkine (MK), a growth factor with neurotrophic activities, was examined immunohistochemically in experimental cerebral infarct of rats. From postoperative day 1 to day 7 after the onset of infarct, anti-MK immunoreactivity was observed in the surrounding ischemic zone of the infarct but not in the necrotic lesion. The immunoreactive material was identified to be MK by Western blotting. On day 14, anti-MK immunoreactivity became negative. Absence of MK in the normal brain was verified both by immunohistochemical staining and Western blotting. The induced expression of MK is an early event: increased expression of glial fibrillary acidic protein (GFAP), a marker of astrocytes, started on day 4 and continued to day 14. These findings suggest that MK is produced around the site of nerve damage and plays a role as a reparative neurotrophic factor during the early phase of cerebral infarct.