INTRUDUCTIONS: Unpredictable significant blood loss is encountered in cases of severe traumas or major surgeries. A quicker recovery of hemoglobin (Hb) would reduce or eliminate the possibility exposing to allogeneic transfusion. The purpose of this study is to evaluate the effects of parenteral iron on experimental acute severe anemia. METHODS: 50 Sprague-Dawley rats, weighing 350g, were used in the study. Blood was removed through the carotid catheter and replaced by 6% hetastarch sodium. The Hb was reduced 50% on first day. The following day, blood depletion continued until Hb were reduced to 30% (4mg/dL) of that of normal rats. Blood pressure and heart rate were maintained within normal range. The anemic rats were randomly divided into two groups: the control group without any treatment and the iron group, in which the high dose (3mg/kg/day) of Iron dextran was given i.v. daily for 10 days postphlebotomy. Hb, hematocrit (Hct), and reticulocyte counts (Ret) as wen as serum iron were tested from baseline to 28 days postphlebotomy. RESULTS: Hb in both groups showed a gradual increase. The Hb in the iron group grew faster than that in the control group between days 6 and 10 (p < 0.05). It took 12 or 14 days (the iron-treated group, the control group, respectably) for Hb s recovery to normal range. Hct were higher in the iron therapy group than those in the control group (p < 0.05) between days 5 and 10. The Ret in the two groups increased after phlebotomy. Ret in the iron therapy group remained higher than those of the control group (p < 0.05) between days 3 and 7. The decrease of circulating iron after phlebotomy was induced. Once replenished with parenteral iron, circulating iron was higher than that of the control group (p < 0.05). CONCLUSIONS: Parenteral iron in large doses can maintain the higher levels of serum iron, increase the Ret, elevate the Hb and Hct faster, and shorten the recovery period after acute severe anemia. It reduces the possibility of allogeneic blood exposure. Also, we speculate that iron has two different roles in increasing Hb concentration: 1) iron is a substrate for heme synthesis, and 2) iron directly modulates the process of erythropoiesis.