Background:Oxidative stress plays an important role in fetus brain development.The aim of this study was to investigate the protective role of melatonin against the effect of caffeine(given 30 mg/kg and 60 mg/kg)in embryo brain.Material and Methods:For this purpose,35 adult female Sprague-Dawley rats were used in the study.Pregnant rats were detected by vaginal smear test and were divided into seven groups with five rats per group.Thirty(30)mg/kg and 60 mg/kg caffeine were administered to the experimental groups between the 1st and 20th days of pregnancy,while melatonin(10 mg/kg)was administered to the treatment groups in addition to caffeine.On the 20th day of pregnancy,fetuses were taken by cesarean section and their weights/lengths were measured.Results:Superoxide dismutase(SOD),glutathione(GSH),glutathione disulfide(GSSG),total antioxidant status(TAS),thiobarbituric acid reactive substances(TBARS),calcium(Ca)and vitamin D(Vit D)levels were measured by spectrophotometric methods.Oxidative stress index(OSI)and total glutathione(GSH/GSSG)levels were the markers used for oxidative stress and measured by TOS/TAS and GSH/GSSG,respectively.All data were statistically evaluated.Conclusion:In this study,it was observed that high dose caffeine reduces oxidative stress in brain tissues while increasing the antioxidant level.