Activation of transcription factor NF-κB plays a critical role in immune, inflammatory and cell death responses. In resting cells, NF-κB is sequestrated in the cytoplasm in an inactive form through its association with inhibitory proteins, IκB (e.g.IκB-α). In response to cell activation, IkB is degraded causing release of active NF-κB. Active NF-κB translocates into the nucleus leading to activation of transcription that may have a profound effect on cell survival, including that after ischemic stroke. Here, using Western blot analysis, we show that immunoreactivity to the major subunit of NF-κB, p65, as well as to the inhibitory subunit IκB-α is equally markedly decreased in the ischemic core after transient middle cerebral and common carotid artery occlusion in rats. In contrast, penumbral regions display no change in p65, and significant increase in IκB-α immunoreactivity, as compared to non-ischemic areas. In these penumbral regions with elevated IκB-α immunoreactivity, we find reduced cytosolic and increased nuclear IκB-α staining of neurons, as determined by immunohistochemistry. Altogether, these results suggest that an altered ratio between activating and inhibitory NF-κB pathways mediated through IκB-α may play an important role in survival of the ischemic penumbra.