Base deficit (BD) has been shown to be a sensitive measure of the degree and duration of inadequate perfusion. We developed a rat model of hemorrhagic shock based on achieving a fixed BD of 13 +/- 1 mmol/L before resuscitation. Using this model, we compared the efficacy of resuscitation with lactated Ringer's solution (LR), Haemaccel (a colloid), and whole blood with that of diaspirin cross-linked hemoglobin (DCLHb, Baxter Healthcare Corp.) by evaluating improvements in BD and restoration of base excess (BE, positive correlate of BD) for 60 minutes following resuscitation. The DCLHb was superior to LR and Haemaccel in restoring and maintaining BE following resuscitation, and was able to restore BE as rapidly as whole blood at half the volume. At 60 minutes, DCLHb at twice the shed blood volume maintained BE at higher (more positive) values compared with all other treatment groups. We conclude that DCLHb is at least as effective as whole blood and superior to LR and Haemaccel in restoring BE within the first 60 minutes following resuscitation in this hemorrhagic shock model.