Zebrafish represent an attractive system for the study of neurogenesis following injury because, unlike mammals, they regenerate damaged neurons. After stab lesioning, initial cell death is followed by a robust inflammatory response 1-2 days post-injury and a marked increase in proliferation of radial glia-like progenitors that peaks 3-4 days post-injury. In order to study the role of the early inflammatory response on neurogenesis, we ablated microglia that responded to injury though concurrent injection of liposomes containing Clodronate at the injury site. Phagocytosis and subsequent degradation of the liposomal membrane releases Clodronate and causes microglial apoptosis. In the absence of microglia, proliferation and neurogenesis were markedly reduced. These effects persisted over time, resulting in incomplete repair in Clodronate-treated, lesioned brains compared to control liposome-treated, lesioned brains. These results indicate that the early inflammatory response following telencephalic lesioning is an important signaling event that stimulates neurogenesis and repair of adult zebrafish brain injury. A significant limitation of Clodronate treatment is that the critical time period during which microglia crucially affect regeneration cannot be determined. Microglia are dependent on colony-stimulating factor receptor 1 (CSFR1) for viability in other organisms. We used a small molecule inhibitor of CSFR1 to determine the effects of non-invasive microglial ablation on regeneration following brain injury and to further determine with increased precision the time period during which microglia are required to stimulate the neurogenic response following injury.