Purpose of review: This review focuses on the latest mechanistic understanding of the effects of estradiol on the splanchnic circulation and the possibility of estradiol treatment as an adjunct for the treatment of trauma-hemorrhage and sepsis. Recent findings: Systemic hypotension induced by shock accompanies marked alterations in blood flow to various organs. Decreased splanchnic perfusion is frequently observed after insults, such as severe hemorrhage or sepsis, which leads to the destruction of the intestinal mucosal barrier and hepatic dysfunction. Studies suggest that estradiol acts as a facilitator of the intestinal blood flow via the increased production of nitric oxide, decreased production of vasoconstrictors, attenuated neutrophil adhesion, and decreased formation of oxygen free radicals. Summary: Trauma-hemorrhage results in decreased circulating blood volume. In contrast, sepsis is an inflammatory state mainly mediated by bacterial products. However, these divergent insults show similar pathophysiologic alterations in terms of the splanchnic circulation. Because estradiol effectively protects the organs from circulatory failure after various adverse circulatory conditions, many studies are being performed to clarify the molecular mechanism of estradiol action with regard to tissue circulation. Estradiol improves the macro- and microcirculation of the splanchnic organs by multiple mechanisms. Nonetheless, it remains unclear which mechanism plays the most important role in the treatment of trauma-hemorrhage and sepsis. Additional studies are required to elucidate the precise mechanism of estradiol action and to determine the usefulness of estradiol treatment for severe hemorrhage and sepsis in patients.