Although several clinical studies show a gender dimorphism of immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis, there are conflicting reports on the role of gender in outcomes. In contrast, results obtained from experimental studies clearly support the suggestion that gender plays a significant role in post-injury pathogenesis. Studies performed in a rodent model of trauma-hemorrhage have confirmed that alterations in immune and organ functions after trauma-hemorrhage are more markedly depressed in adult males and in ovariectomized and aged females; however, both are maintained in castrated males and in proestrus females. Moreover, the survival rate of proestrus females subjected to sepsis after trauma-hemorrhage is significantly higher than in age-matched males or ovariectomized females. In this respect, organ functions and immune responses are depressed in males with sepsis or trauma, whereas they are unchanged or are enhanced in females. This article reviews studies delineating the mechanism by which estrogen regulates cerebral nervous, lung, and heart systems in an experimental model of sepsis, trauma, or reperfusion injury. © 2012 Japanese Society of Anesthesiologists.