Angiogenesis, the formation of new blood vessels, has been studied following injection of platelet-activating factor into the rat striatum. Immunohistochemical analysis for laminin showed that platelet-activating factor induced significant neovascularization in the striatum. A dose-dependent loss of striatal neurons accompanied this angiogenic activity. The platelet-activating factor-induced neovascularization and neurodegeneration were attenuated by the platelet-activating factor receptor antagonist, BN52021, or the inducible nitric oxide synthase inhibitor, aminoguanidine. Additionally, these agents significantly reduced levels of the angiogenic agent vascular endothelial growth factor, which was markedly enhanced in platelet-activating factor-injected striatum. Double immunofluorescence staining demonstrated that expression of vascular endothelial growth factor and inducible nitric oxide synthase were predominantly localized to microglia, suggesting that inflammatory responses mediated by activated microglia could contribute to platelet-activating factor-induced angiogenesis and neuronal loss.