PURPOSE: The purpose of this study was to evaluate the role of mast cell and histamine as typical product of mast cell in ischemia-reperfusion injury of muscle flap using H2 receptor blocker and mast cell stabilizer. METHODS: Thirty-five Sprague-Dawley rats weighing 250-300 gm were divided into four groups; Group I: Control group without ischemia, Group II: Normal saline injection group with ischemia, Group III: Cimetidine injection group with ischemia, Group IV: Sodium cromoglycate injection group with ischemia. Well established single pedicled transverse rectus abdominis musculocutaneous(TRAM) flap was designed in all rats and were rendered ischemia by clamping the artery for 150 minutes. All injections were applied intramuscular around gluteal area 30 minutes before reperfusion. The flap survival was evaluated at 7 days after operation. Neutrophil counts and mast cell counts were evaluated 24 hours after reperfusion. RESULTS: The difference of skin flap survival between control group and cimetidine injection group was not significant. In the normal saline injection group flap survival was markedly decreased compared to that of control group. The muscle flap survival was similar to the results of skin flap survival. The neutrophil counts were significantly decreased in control group and sodium cromoglycate injection group than normal saline injection group. The mast cell counts were significantly decreased in cimetidine injection group and control group than both normal saline injection and sodium cromoglycate injection groups. The protective effect of sodium cromoglycate was not seen in the skin flap, but the muscle flaps showed protective effects of sodium cromoglycate compared to normal saline injection group. CONCLUSION: It is suggests that commonly used antihistamine(H2 receptor blocker) has protective effect against ischemia-reperfusion injury to skin and muscle flaps by reducing neutrophil and mast cell. The mast cell stabilizer was not effective for skin flap but, possibly, for muscle flap.