Microglia have myriad roles in the central nervous system additional to their immune ones. However, their functions in the healthy adult remain poorly understood. To understand how microglia contribute to regulating satiety, feeding and cognitive function in healthy individuals, we developed a Wistar rat with a diphtheria toxin receptor in the promoter region for the fractalkine receptor (Cx3cr1), which is expressed on microglia and monocytes. This model allows acute microglial and monocyte ablation (followed by repopulation) upon application of diphtheria toxin, enabling us to directly assess microglial function. Short-term microglial ablation in these rats leads to a dramatic weight loss that is largely accounted for by an acute reduction in food intake, with these rats showing a particular aversion to highly palatable food. This weight loss and anorexia are not likely due to a sickness response since the rats do not display peripheral or central inflammation, withdrawal, anxiety-like behavior, or nausea-associated pica. Hormonal and hypothalamic anatomical changes are largely compensatory to the suppressed food intake, which occurs in association with disruption of the gustatory circuitry at the paraventricular nucleus of the thalamus. With this model, we also show that cognition in the novel object and place recognition tasks is entirely unaffected by acute microglial ablation. However, when microglia repopulate the brain, learning and memory performance in these tasks is improved. This transitory cognitive enhancement is associated with an ameboid morphology in the newly replaced microglial cells as well as with differences in synaptic markers and the density of mature hippocampal synaptic spines. Together these data indicate that microglia are important for supporting normal feeding behaviors, as well as learning and memory. They suggest these cells may be a useful potential target for satiety control and to strategically enhance memory; and that our understanding of microglia needs to be expanded.