In trauma, infection and hemorrhagic shock derived stress, primary and secondary injury may result in severe derangement in the internal environment. The abnormal changes of immune-mediated inflammation interfere its pathogenesis and development directly. In recent years, various aspects of neuroendocrine responses, especially the regulatory effects of hypothalamic-pituitary-adrenal and sympathetico-adrenomedullary axes in inflammatory diseases have been the focus of research. Most importantly, corticotropin-releasing hormone (CRH) acts as a key player in the regulation of interactions between neuroendocrine and immunity both directly and indirectly. The paper summarized the recent development of CRH in the immune-mediated inflammation.