Estrogen is a sex hormone that plays different roles in the brain versus in the periphery. Notably, low levels of estrogen have been shown to be associated with spatial memory impairment and object recognition impairment. Microglia are resident immune cells in the brain, responsible for pruning synapses and responding to tissue injury. A lower presence of estrogen has been shown to minimize their typical function. With strong spatial memories, mice are a suitable model organism for studying the effects of low estrogen states on the mammalian brain. We studied twenty female mice with ten belonging to a control group and ten that received letrozole, which is an aromatase inhibitor that induces low-estrogen states in the brain. The region of interest was the stratum radiatum in the hippocampus. Immunohistochemistry was the primary method used and is the application of antibodies to a tissue layer to demarcate a particular antigen. Our projects applied IHC to stain for protein markers CD68 and PSD-95. We hypothesized that the letrozole group would have lower amounts of CD68 and PSD-95 integrated density. With respect to PSD-95, we found that the integrated density PSD-95 was significantly lower in the letrozole group than in the control group in a subset of the data. When staining for CD68, we found a decrease in the integrated density of CD68, emphasizing decreased microglial activation with lower estrogen. Given these results, we demonstrate a clear relationship between low estrogen states in the adult female mouse hippocampus and lower microglial activation.