A surface-modified polyethyleneglycol-conjugated human hemoglobin (MP4) and alpha alpha-cross-linked human hemoglobin (Hb) were used to restore oxygen carrying capacity in conditions of extreme hemodilution (hematocrit 11%) in the hamster window model preparation. Changes in microvascular function were analyzed in terms of effects on capillary pressure and functional capillary density (FCD). MP4, at 1.0 ± 0.2 g/dl_blood concentration significantly lowered mean arterial pressure (MAP) below baseline (99.6 ± 7.6 mmHg) to 82.4 ± 6.9 mmHg (P < 0.05), and decreased of FCD to 70 ± 9%. Hb caused a greater recovery in MAP to 94.4 ± 6.2 mmHg and lowered FCD to 62 ± 8%. However, differences between Hb and MP4 in FCD were not statistically significant. Capillary pressures were in the ranges of 17 - 21 mmHg for MP4 and 15 - 19 mmHg for Hb, with both significantly lower than baseline (P < 0.05). Pressure in 80 µm diameter arterioles was significantly increased with Hb relative to MP4 (P < 0.05). These results were compared to previous findings on the relation between capillary pressure and FCD, they support the concept of a relationship between FCD and capillary pressure. Measurement of changes in arteriolar diameter, microvascular blood flow and FCD show that there was no statistical difference between using Hb and MP4 in extreme hemodilution. Microvascular resistance in arterioles with diameter range of 70 - 80 µm, showed an increase relative to control with Hb, while MP4 caused a decrease.