AIM:To study the protective effect of a natural antioxidant, melatonin, against multistress condition induced lipid peroxidation via determination of gastric damage and plasma malondialdehyde (MDA) level by high performance liquid chromatography in rats. METHODS:We compared indomethacin-induced gastric damage and MDA plasma level in three groups of rats: unoperated, bile duct ligated and sham-operated and evaluated the role of the melatonin on gastric damage and plasma MDA level. Indomethacin and melatonin were injected intraperitoneally in doses of 50 mg/kg and 20 mg/kg, respectively. Animals were killed 4 h after indomethacin injection. RESULTS:Indomethacin induced more severe gastric damage and plasma MDA level in bile duct ligated animals was significantly higher (3.1 ± 0.04 µmol/L) than sham (2.8 ± 0.04 µmol/L) and unoperated animals (1.4 ± 0.08 µmol/L). Pretreatment with melatonin reduced indomethacin-induced gastric damage and plasma MDA level. CONCLUSION:Considering the results of this study, we suggest that in multistress conditions the intensity of gastric damage and the plasma MDA level are great and melatonin reduces the negative effect of lipid peroxidation and cell damage by oxidative stress in multistress conditions due to its antioxidizing activity.