The proposed mission to Mars will expose astronauts to space radiation that is known to adversely affect cognition and tasks that rely on fine sensorimotor function. Space radiation has also been shown to affect the microglial and neurogenic responses in the central nervous system (CNS). We recently reported that a low dose of 5 cGy 600 MeV/n ²⁸Si results in impaired cognition and skilled motor behavior in adult rats. Since these tasks rely at least in part on the proper functioning of the striatum, we examined striatal microglial cells in these same subjects. Using morphometric analysis, we found that ²⁸Si exposure increased activated microglial cells in the striatum. The majority of these striatal Iba1⁺ microglia were ED1^–, indicating that they were in an alternatively activated state, where microglia do not have phagocytic activity but may be releasing cytokines that could negatively impact neuronal function. In the other areas studied, Iba1⁺ microglial cells were increased in the subventricular zone (SVZ), but not in the dentate gyrus (DG). Additionally, we examined the relationship between the microglial response and neurogenesis. An analysis of new neurons in the DG revealed an increase in doublecortin-positive (DCX⁺) hilar ectopic granule cells (hEGC) which correlated with Iba1⁺ cells, suggesting that microglial cells contributed to this aberrant distribution which may adversely affect hippocampal function. Taken together, these results indicate that a single dose of ²⁸Si radiation results in persistent cellular effects in the CNS that may impact astronauts both in the short and long-term following deep space missions.