Extracellular signal-regulated kinase (ERK) pathways play a crucial role in cell growth and long-lasting neuronal plasticity. Several studies have shown that phosphorylated-ERK (p-ERK) significantly increases after kainic acid (KA) administration. However, little or no information is available about the spatial distribution of p-ERK after KA-induced seizures. We herein show that KA-induced seizures significantly increase p-ERK in both neurons and astrocytes in rat brain using Western blots and immunohistochemistry. A strong immunoreactivity for p-ERK was induced in the dentate hilar neurons and CA3 neurons 30 mins and 6 hrs after KA injection. In addition, immunoreactivity for p-ERK was seen in astrocytes 6 hrs after KA injection. 72 hrs after KA injection, all pyramidal neurons had died. These findings suggest that the ERK pathway participates in the KA-induced neurotoxicity in the rat hippocampus.