GADD45 is a DNA damage-inducible gene that accelerates DNA excision repair and can be induced by a variety of DNA-damaging stimuli in mammalian cells. We investigated the expression of GADD45 mRNA and protein using in situ hybridization and immunocytochemistry in rat brains after 2 h of temporal focal ischemia. The expression of GADD45 mRNA was induced in neurons throughout ischemic cortex 4 h after the onset of ischemia but was restricted to ischemic penumbra regions at 24 h after ischemia. The expression of GADD45 protein was increased only in sublethally injured neurons in the penumbra regions at both 4 h and 24 h following ischemia. These results suggest that GADD45 could have a protective role in ischemic neurons.