The focal ischemia obtained in an animal model of middle cerebral artery occlusion (MCAo) causes the "core" of damage in the striatum and the "penumbra" of damage in the fronto-parietal cortex. The latter is mainly functionally affected and shows changes in nNOS and iNOS expression during the acute phase of ischemia. With the aim to study possible relationships between these changes and the affection entity during the animal recovery, we investigated from 24 up to 144 h after reperfusion the expression and content of these two NOS isoforms in the neurons and microglia and the degree of microglia reactivity in the fronto-parietal cortices of rats undertaken to transient MCAo. Evaluation of motor-sensory performances and survival allowed dividing the animals into two groups. Immunohistochemistry, western blot and quantitative analysis demonstrated, both in the ischemic and contralateral cortex of the rats with longer survival, wellness and significantly increased number of the nNOS-IR neurons at 24 h and moderately activated microglia up to 144 h. In the rats not recovering, injured and significantly decreased nNOS-IR neurons, intensely activated microglia and appearance of iNOS-IR were seen at all time points. In conclusion, since the recovery occurs when nNOS-IR neurons are greatly increased, we presume nNOS protect the tissue likely controlling the passage from the state of reactive to that of activated microglia. Moreover, the morphological signs of wellness and the two-fold increase in number of the nNOS-IR neurons appear to be characteristic of the "penumbra" area and could explain why this region is mainly functionally affected.