Inhibitor of DNA binding (ID) proteins bind to and inhibit the function of basic helix-loop-helix transcription factors, including those that regulate proliferation and differentiation during development. However, little is known about the role of ID proteins in glial activation under neuropathological conditions. In this study, we evaluated the expression of ID4 following induction of excitotoxic lesions in mouse brain by kainic acid injection. The number of ID4-expressing astrocytes increased in the CA1 layer of the injured hippocampus until 3 days post-lesion. To analyze the effects of ID4 on cell proliferation, primary astrocytes were transduced with recombinant adenovirus expressing GFP-ID4. Overexpression of ID4 led to increased proliferation of astrocytes. These results suggest that ID4 plays a proliferative role in astrocyte activation after excitotoxin-induced hippocampal neuronal death.