Hypothesis: Ischemic rat epigastric adipocutaneous flaps, which are conditioned before being raised by remote ischemic preconditioning (RIPC), have greater survival than flaps that are preconditioned after being raised. RIPC induces phosphorylated p38 MAP kinase which may correlate with improved flap survival. Methods: Female Wistar rats had 8 x 12 cm abdominal adipocutaneous flaps raised on the medial branch of the superficial epigastric artery. Group I (Controls, n=10) had the flap elevated and pedicle clamped for 3 hours, then closed with a sheet of plastic between the flap and the abdominal wall. Group II (n=6) had RIPC by a tourniquet on the contra-lateral hind limb before the flap was dissected. Group III (n=5) mimicked Group II plus had an infusion of N-nitro-L-argine methyl ester, a nitric oxide blocker, (L-NAME, 10 mg/kg) beginning 5 minutes prior to the RIPC. Group IV (n=6) had the flap elevated prior to the RIPC of the hind limb. All groups, except controls, had 10 minutes of RIPC with 30 minutes of reperfusion, then ischemia. Tissue samples were taken at distal margins of the flap before preconditioning, 30 minutes after preconditioning and after prolonged flap ischemia to detect levels of phosphorylated p38 MAP kinase. Results: Group II with RIPC before the flap was lifted had less tissue necrosis compared to controls (39.8 ± 9.7 compared to 9.3 ± 2.5 % survival) and less tissue necrosis than Group IV where the flaps were raised before the RIPC (13.5 ± 3.9 %). The difference between Group II and Group IV was statistically significant (p<0.01). Pre-infusion of L-NAME in Group III before RIPC blocked the survival advantage conferred by the preconditioning (8.4 ± 2.0 %). Flaps treated with RIPC exhibit a modulation in phosphorylated p38 MAP kinase in samples collected 30 minutes after RIPC. Conclusion: Rat epigastric adipocutaneous flaps elevated after RIPC have greater survival following prolonged ischemia than flaps, which are raised prior to the RIPC. Blocking the nitric oxide pathway removes the survival advantage conferred by ischemic preconditioning. Modulation of phosphorylated p38 MAP kinase may represent a protection pathway for ischemic preconditioning.