Microglia, the resident immune cells of the central nervous system (CNS), are activated by various stimuli. Resting microglia are the basis of normal neurogenesis, while activated microglia may inhibit neurogenesis through the production of pro-inflammatory mediators and cytokines. Recent research suggests that microglia are activated by irradiation. This may play a role in radiation-induced brain injury (RIBI). DNA double-strand breaks (DSBs), the most deleterious form of DNA damage after ionizing radiation, may rapidly trigger the activation of the NF-kappaB pathway via p53-induced protein leading to the release of pro-inflammatory mediators and cytokines. Thus, a negative regulator of the NF-kappaB pathway that inhibits radiation-induced microglia activation could be used to treat RIBI. Corilagin, a member of the tannin family, inhibits NF-kappaB pathway activation. In the present study, we examined the inhibitory effects of corilagin on radiation-induced microglia activation using a variety of techniques. Our data suggest that corilagin inhibits radiation-induced microglia activation via suppression of the NF-kappaB pathway and the compound is a potential treatment for RIBI.