Objectives: Using a new fluorescence-quenching optode which, unlike earlier oximeters, neither consumes oxygen nor generates heat, we sought to determine the effects of hemorrhage and resuscitation on subcutaneous Po-2. Additionally, we compared the effects of resuscitation with diaspirin crosslinked hemoglobin, an oxygen-carrying solution, on subcutaneous Po-2 to that of traditional resuscitative fluids. We also compared mean arterial pressure and central venous oxygen saturation, indirect indices of perfusion, to subcutaneous Po-2, a direct index of perfusion. Design: Prospective trial, randomized for selection of treatment regimen. Setting: Shock-trauma laboratory of a medical university. Subjects: Male Sprague-Dawley rats, weighing 260 to 380 g. Interventions: Rats were bled 22 mL/kg and resuscitated, 1 min later, with either 66 mL/kg of lactated Ringer's solution, 22 mL/kg of human serum albumin, 22 mL/kg of blood, or 22 mL/kg of diaspirin crosslinked hemoglobin. A fifth group of animals was not resuscitated after hemorrhage. Subcutaneous Po-2 and mean arterial pressure were monitored continuously throughout the experiment, while central venous oxygen saturation was measured intermittently. Measurements and Main Results: Subcutaneous Po-2 decreased in response to hemorrhage and, although it did increase after resuscitation with each fluid, no treatment was able to restore subcutaneous Po-2 to baseline within 2 hrs postresuscitation. Subcutaneous Po-2 continued to decrease after hemorrhage in the unresuscitated animals. In contrast, mean arterial pressure was restored to baseline values in only blood- and diaspirin crosslinked hemoglobin-treated animals, although this effect was lost within 30 mins in the blood-treated group. Only blood restored the central venous oxygen saturation to baseline values in the early postresuscitation period. Conclusions: The fluorescence-quenching optode consistently followed changes in subcutaneous Po-2 during hemorrhage and after resuscitation. Diaspirin crosslinked hemoglobin performed as well as blood in restoring peripheral perfusion, as measured by subcutaneous Po-2, while both of these fluids were superior to either lactated Ringer's solution or albumin. Both whole blood and diaspirin crosslinked hemoglobin restored mean arterial pressure to baseline, although the effect of the latter was of a longer duration. The presser effect of the crosslinked hemoglobin did not affect peripheral perfusion, as reflected by the values for subcutaneous Po-2. Subcutaneous Po-2 is a useful adjunct in assessment of the adequacy of peripheral perfusion and may help redefine targets for resuscitation.