The effect of the cytokine, colony stimulating factor-1 (CSF-1), on neuronal survival in cerebral cortex ischemic lesion was determined. Ischemic lesions were made in C3H/HeJ mice by disrupting blood vessels that penetrate the cerebral cortex from the pial-vascular plexus. Recombinant human colony stimulating factor 1 (rhCSF-1) was delivered in chitosan microcapsules that were either implanted intraperitoneally 2 weeks before surgery or at the site of the lesion at the time of surgery. Neuronal survival was twofold greater and the size of the infarct was considerably smaller in animals that received rhCSF-1-containing microcapsules. There was no significant difference whether the microcapsules were implanted intraperitoneally or at the site of the lesion. We found that CSF-1 receptor (c-fms) was upregulated in neurons at the site of the lesion and we propose that neuron rescue in ischemic damage is potentiated by CSF-1 signaling through CSF-1 receptor in the neurons.