Introduction: The release of harmful pollutants, especially heavy metals in the environment and the contact of various types of metal toxins with humans, animals and plants lead to create oxidative stress and harmful effects on human and animal health. Oxidative stress plays an important role in various diseases, especially liver diseases, in order to help people's health conditions and protect them against free radicals of heavy metals as the main factors in oxidative stress and liver damage, researchers are recommended the use of diet food including fruits and vegetables containing antioxidants as the best way to deal with oxidative stress. This research was performed with the aim of the investigation of protective effects of Achillea Wilhelmsi aqueous and hydroalcoholic extracts on oxidative damage caused by trivalent arsenic in isolated rat hepatocytes. Materials and methods: Hepatocytes were prepared from rat liver using the perfusion method with collagenase and finally, the protective effect of Achillea Wilhelmsi aqueous and hydroalcoholic extracts on arsenic-induced cytotoxicity by measuring cytotoxicity markers, ROS production and lipid peroxidation and potential drop percentage of the mitochondrial membrane were investigated. In order to induce toxicity, arsenic trioxide with EC50,2h (Concentration 50 µM) was used. Results: Arsenic trioxide with a concentration of 50 µM could during 3 hours of incubation lead to severe cytotoxicity, increased ROS production, increased lipid peroxidation, increased potential drop percentage of mitochondrial membrane and lysosome membrane damage compared to the control group (P<0.05). In all the tests, the toxicity marker induced by arsenic was inhibited by all the concentrations used of Achillea Wilhelmsi aqueous and hydroalcoholic extracts (P<0.05). Conclusion: It seems that these extracts in appropriate concentrations and amounts can be effective in reducing liver toxicity caused by arsenic.