Inflammation is a complex biological response mediated by macrophages to protect the body from the pathogens and danger signals. The inflammatory response is initiated by priming, a process increasing the expression of inflammatory genes by extracellular pattern-recognition receptor (PRR)-mediated detection of pathogens, followed by triggering, a process detecting cytosolic pathogens by intracellular PRRs. Triggering induces the formation of intracellular PRR complexes called inflammasomes composed of two main groups; canonical and non-canonical inflammasomes. Unlike canonical inflammasomes, non-canonical inflammasomes were recently discovered, and the knowledge of the roles of non-canonical inflammasomes in inflammatory responses and human diseases is not still enough. Mouse caspase-11 and human caspase-4/5 were identified as non-canonical inflammasomes, and many efforts have been made to demonstrate the regulatory functions of these non-canonical inflammasomes in inflammatory responses and several human diseases. This review discusses the recent research progress to understand the roles of the caspase-11 non-canonical inflammasome in macrophage-mediated inflammatory responses, which can provide the insight and contribute to developing potential diagnostic and therapeutic agents to prevent and treat human infectious and inflammatory/autoimmune diseases.