Abstract: Ischemic postconditioning is a useful manipulation to reduce the undesirable effects of ischemia-reperfusion (I/R) injury. The beneficial results of this phenomenon against I/R injury have been seen in several flap models. However, there are no published works comparing different postconditioning (post-con) cycles in skin flaps. In this study, we investigated the effectiveness of different post-con cycles in a skin flap model. Epigastric island flap (6 × 3 cm) model which was based on the left superficial epigastric artery and vein was used, and complete 6 hours of ischemia was generated by occlusion of the pedicle. Forty male Wistar rats were allocated into 5 groups (n = 8 in each group). Group 1 (sham group): the elevated skin flap was repositioned without an episode of ischemia. Group 2 (control group): skin flap was elevated and 6 hours of complete ischemia was induced by clamping the pedicle. Group 3 (post-con 1): After ischemia, post-con was performed by 6 cycles of 15 seconds of repeated I/R periods. Group 4 (post-con 2): After ischemia, post-con was performed by 6 cycles of 30 second of repeated I/R periods. Group 5 (post-con 3): After ischemia, post-con was performed by 6 cycles of 60 second of repeated I/R periods. Flap viability was assessed 1 week after the surgical procedure, the necrotic area of the skin flap was measured using image analysis on the computer. The area of flap necrosis was statistically significant between the control and post-con group 4 and group 5, and no statistically significant difference was obtained between the control and post-con group 3. Groups 4 and 5 demonstrated lesser area of flap necrosis than the control group and group 4 was superior to group 5. The results revealed that the post-con applied by means of 6 cycles of 30 seconds yields the best protection against I/R injury in the rat skin flap model.