Background and Aim: Cutaneous flaps are frequently used in plastic surgery and ischemic necrosis is still a complication as a clinical problem. Different methods have been attempted in order to enhance flap survival including: hyperbaric oxygen, angiogenesis therapy (FGF, VEGF), pharmacologic agents such as sympatholitic, vasodilators, calcium channel blockers, hormonal agents, prostaglandin inhibitors, anticoagulants, oxygen-derived free radical scavengers, corticosteroids, delayed flap surgery, etc. In an experimental study it has been observed that topical application of oleic acid postoperatively on random skin flap increases survival of the flap. We have investigated the effect of prophylactic use of oleic acid on the survival of the rabbits’ random skin flap. Materials and Methods: A total of 46 adult white New Zealand rabbits having a 3×10.5cm dorsal thoracic skin flap were selected. Flaps were assigned in 3 groups: for the first group topical oleic acid 75% (10% by volume) was applied ipsilaterally, while for the second group it was applied contralaterally and in the third group (control) the dorsal flap was treated with a basic ointment (a medical pure Vaseline). Having elevated each flap, it was sutured into its bed. On the 6th postoperative day, area of flap survival was measured based on clinical evaluation. Results: The average of total skin flap survival was 11 cm2 in the first, 13.2 cm2 in the second (p=0.65), and 20.7cm2 in third group (control) (p<0.05). Conclusion: Although skin flap survival increases when topical oleic acid is used after surgery and flap elevation, prophylactic use of topical oleic acid decreases flap survival in the rabbits’ random skin flap.