The mannose receptor is a pattern-recognition receptor involved in innate and adaptive immunity. The receptor is mainly expressed by macrophages and, within the brain, by astrocytes and microglia. This study reports for the first time the effects of two classical proinflammatory (interferon-gamma, IFNgamma) and anti-inflammatory (interleukin-4, IL-4) cytokines on the levels of expression and activity of the mannose receptor expressed by mouse microglia, the brain resident macrophages. As observed for macrophages, IFNgamma treatment led to a decrease and IL-4 to an increase of mannose receptor expression. Consequently, the rates of pinocytosis were strongly upregulated by IL-4 and inhibited by IFNgamma. This latter, however, resumed with time and reached again the constitutive rate of pinocytosis. This recovery resulted from an increased pinocytic activity of the few mannose receptor molecules still expressed by IFNgamma-treated microglia. This may suggest a brain-specific regulation of the effects of IFNgamma since such a phenomenon has not been observed in macrophages. Together, these observations demonstrate that cytokine-stimulated immunocompetent microglia express a functional mannose receptor.