Aim: Methotrexate, a folic acid antagonist is a chemotherapeutic drug used in the treatment of various inflammatory diseases as well as some cancer types. The purpose of this study; it is the study of the effects of boric acid against the hepatotoxic side effects of methotrexate. Material and Method: Male Wistar albino rats were divided into five groups and each group consisted of six animals. The rats in group 1 were used as a control group. Methotrexate was administered to the rats in group 2 and boric acid to the rats in group 3. While the rats in group 4 were given first methotrexate and then boric acid, the rats in group 5 were administered boric acid first and then methotrexate. Results: Light microscopic examination revealed sinusoidal dilatation, hepatocyte degeneration, vascular congestionthrombosis, and inflammatory infiltration in the livers of rats treated with methotrexate. It was observed that the protective effect of boric acid was more effective than its treatment. In the groups given methotrexate, the level of oxidative stressrelated parameters such as lipid hydroperoxide, MPO and disulfide increased (p<0.05 for all parameters), whereas the level of antioxidant parameters such as native thiol, total thiol and catalase decreased (p<0.05 for all parameters). Conclusion:In this study, the protective effect of boric acid was found to be higher than the therapeutic effect in liver damage caused by methotrexate. Oxidative hepatotoxicity resulting from methotrexate application disrupted the thiol disulfide balance and caused a shift to the oxidation side.