sex differences in early postnatal microglial colonization of the developing rat hippocampus following a singleday alcohol exposure microglia are involved in various homeostatic processes in the brain including phagocytosis apoptosis and synaptic pruning sex differences in microglia colonization of the developing brain have been reported but have not been established following alcohol insult developmental alcohol exposure represents a neuroimmune challenge that may contribute to cognitive dysfunction prevalent in humans with fetal alcohol spectrum disorders fasd and in rodent models of fasd most studies have investigated neuroimmune activation following adult alcohol exposure or following multiple exposures the current study uses a single day binge alcohol exposure model postnatal day pd 4 to examine sex differences in the neuroimmune response in the developing rat hippocampus on pd5 and 8 the neuroimmune response was evaluated through measurement of microglial number and cytokine gene expression at both time points male pups had higher microglial number compared to females in many hippocampal subregions on pd5 but this difference disappeared by pd8 unless exposed to alcohol expression of proinflammatory marker cd11b was higher on pd5 in alcoholexposed ae females compared to ae males after alcohol exposure cc motif chemokine ligand 4 ccl4 was significantly increased in female ae pups on pd5 and pd8 tumor necrosis factor tnf levels were also upregulated by ae in males on pd8 the results demonstrate a clear difference between the male and female neuroimmune response to an ae challenge which also occurs in a timedependent manner these findings are significant as they add to our knowledge of specific sexdependent effects of alcohol exposure on microglia within the developing brain