Glucagon infused into Macaca rhesus monkeys in hypovolemic shock significantly improved splanchnic microcirculatory perfusion, increased pH, and decreased phosphate, lactate, amino acid, and fatty acid levels as compared to the controls. Further, in vitro rat liver perfusion studies showed that glucagon significantly increased lactic acid extraction, even after reducing oxygen pressure and perfusant flow to a minimum. Thus, in addition to its cardiotonic and vasodilatory effects, glucagon was shown in this study to improve perfusion in the splanchnic microcirculation and to decrease anaerobic metabolites. These findings support its use in the treatment of hypovolemic shock.