In the present study, embryonic rat neocortex was implanted into the parietal subcortical area of adult naive animals. On the 7th day, the middle cerebral artery was permanently occluded ipsilateral to the graft. Twenty-four hours after middle cerebral artery occlusion, the extent of infarct was visualized by means of 2,3,5-triphenyltetrazolium chloride histochemistry and quantified in four different standardized coronal plains. Subsequently, the effects of fetal tissue grafting and those of transplantation were identified by using glial fibrillary acidic protein and nerve growth factor immunocytochemistry. The grafts integrated well into their new environment and significantly reduced the size of infarct in middle cerebral artery-occluded animals compared with both sham-operated and control rats 24 h postoperation. The underlying mechanism of this phenomenon might be an increased neurotrophic, particularly nerve growth factor, release by the grafted fetal tissue. Moreover, reactive astroglial cells may also trigger the neuroprotection by additional ischemia-induced nerve growth factor release. The present data demonstrate the potential neurotrophin-mediated protective effects of fetal brain tissue implanted into the adult rat brain before unilateral middle cerebral artery occlusion and the beneficial effects of astrocyte activation.