Microglia derive from mononuclear myeloid progenitors and are a major glial complement of the central nervous system. When microglia are activated they secrete inflammatory cytokines and toxic mediators which amplify the inflammatory response. In addition, the microglia inflammatory products are implicated in the neuronal destruction usually observed in various neurodegenerative diseases. Microglia cells express corticotropin releasing hormone (CRH) receptors, and activation of microglia by CRH releases bioactive molecules which have a biological effect in the brain and regulate several neurological diseases. CRH plays a pivotal role in stress responses and is a key mediator of the hypothalamic-pituitary-adrenocortical system. CRH is expressed in human mast cells, leading to autocrine effects and participates in inflammatory response together with neuropeptides, and stimulates mast cells. IL-33-activated mast cells release vascular endothelial growth factor in response to CRH and act synergistically to increase vascular permeability. CRH also up-regulates IL-18 expression by increasing intracellular reactive oxygen in microglia cells. Here we report the relationship between CRH, microglia and mental disorders.