In this study, it was aimed to investigate the effect of artichoke administration on oxidative stress and antioxidant enzyme activities in blood tissue of methotrexate (MTX) administered rats. Male Wistar-Albino rats were divided into four groups as described; control group, artichoke treated group, MTX treated group and MTX+artichoke treated group. MTX and artichoke applications were started at same time. Artichoke was applied at a dose of 1.5 g/kg/day body weight for 9 days by gavage, while MTX was administered intraperitoneally at a dose of 7 mg/kg/day for 3 days. At the end of the 9-day experiment period, all animals were sacrificed and blood tissue samples were removed into anticoagulant containing tubes. In this study, malondialdehyde (MDA), reduced glutathione (GSH) levels, catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were measured to determine the effects of artichoke on MTX-induced damage. In MTX treated group, MDA levels (P<0.001) were detected to significant increases while GSH (P<0.001) levels, CAT (P=0.001), GSH-Px (P=0.001) and SOD (P<0.001) activities were detected to significant decreases when compared with control group. In MTX+artichoke group, the values of all parameters approached the control group values. When MTX+artichoke group was compared with MTX group, it was observed that MDA and GSH levels decreased, KAT and GSH-Px activities increased, and SOD activities did not change. It was concluded that artichoke can be a natural antioxidant that can be used to reduce toxicity caused by MTX.