Kainic acid (KA)-induced seizure induces the hippocampal cell death. There are reports that AMP-activated protein kinase (AMPK), which is an important regulator of energy homeostasis of cells, has been proposed as apoptotic molecule. In this study, we investigated the altered expression of AMPK cascade in the hippocampus of mice during KA-induced hippocampal cell death. Mice were killed at 2, 6, 24 or 48 h after KA (30 mg/kg) injection. Histological evaluation of KA-treated hippocampus revealed hippocampal cell death first at 6 h and appearing prominently by 48 h after KA injection. Immunoreactivity of Ca(2+)/calmodulin-dependent protein kinase kinasebeta (CaMKKbeta) was increased after KA treatment. In Western blot analysis, AMPK activation was increased 2 h after KA treatment. The proteins of downstream AMPK, including those of glucose transporter1 (GLUT1) and phosphorylation of Acetyl CoA Carboxylase (ACC) were increased in the hippocampus after KA treatment. These results indicate that sustained AMPK activation might be a mechanism by which KA-induced seizure causes hippocampal cell death of mice.