Tissue plasminogen activator (tPA) is used to treat acute stroke, but tPA- and plasminogen-gene-deficient mice exhibit resistance to neurodegeneration. Thus, it is unclear whether the tPA-plasminogen system, an extracellular proteolytic cascade plays a helpful or harmful role, and whether plasminogen is induced by neurodegeneration. In the CA3, kainic acid (KA)-injection caused neuronal damage after 6 h, and almost all of the neurons were lost after 7 days. Plasminogen mRNA was strongly induced 6 h after injection, then gradually decreased, and was very weak at 2 days after injection. Plasminogen protein was expressed after 6 h and localized in abnormally shaped neurons. The in vivo expression of plasminogen was synchronous with morphological changes in neurons. These results suggest that the expression of plasminogen induced by KA-injection may disrupt of neuron-extracellular matrix interaction and thereby contribute to cell death in neurons in the hippocampus.