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Reconstructive procedures with pedicled and free flaps are associated with a risk of ischemia. Prostaglandin E1 (PGE1) is a hormone-like substance with known antiischemic and tissue-protective effects. The aim of this study was to evaluate the effect of PGE1 on the microcirculation in random pattern skin flaps on rats.Twenty-four rats were divided into 2 groups: an intervention group given PGE1 for 6 hours and a control group given saline. The flap (2 × 10 cm) was created on the back of the rats, and the microcirculation was monitored with laser Doppler perfusion imaging in 5 different zones (1, proximal; 5, distal) before surgery and after 60, 180, and 360 minutes postoperatively.Before surgery, there was no difference in the perfusion in any zones between the intervention group and the control group. The mean perfusion values in zone 1 in the intervention group were significantly higher than those in the control group at 60, 180, and 360 minutes postoperatively (P = 0.02, P = 0.05, and P = 0.04, respectively). At 360 minutes, we also found significantly higher levels of perfusion in the intervention group in zones 4 and 5 (P = 0.05 and P = 0.03, respectively) compared with the controls. Comparing the perfusion at 360 to 60 minutes in the intervention group, we found a significant increase in microcirculation in all zones, which were not seen in the control group.PGE1 increased perfusion in the dermal random pattern flaps on rats.