Neuroinflammation is presented in the acute phase brain damage as well as chronic diseases. Cells that are directly or indirectly involved in immune responses compose the central nervous system (CNS). Microglia are resident cells of the CNS and, as peripheral macrophages, are activated in presence of some cellular insult, producing a large number of cytokines and chemokines in order to remove toxins from the extracellular space. This activation can lead to a breakdown of the blood-brain barrier, production of reactive oxygen species that is involved in the progression of CNS damage as occurs in septic encephalopathy. Given the growing relevance of microglia in the area of neurotoxicology, we describe the role of microglia and the cellular mechanisms that activate these cells during sepsis. Thus, in this review we focused on the relationship between microglia and neuroinflammation associated with sepsis.