Introduction: Industrial and environmental pollution, excessive iron supplementation and blood transfusion are among the factors that may cause iron toxicity. Therefore, it is necessary to identify the mechanisms influencing or protecting against iron toxicity. The present study aimed to investigate the protective effects of quercetin as an antioxidant on hepatotoxicity induced by iron oxide and nano-iron oxide. Materials and Methods: The study was conducted on 30 Wistar rats (five groups): A) control group, B) nano-iron oxide, C) iron oxide, D) nano-iron oxide plus quercetin, and E) iron oxide plus quercetin. Nano-iron oxide and iron oxide were administered in daily doses of 20mg/kg, and quercetin in daily doses of 100mg/kg by intraperitoneal injection for 15 days. Correspondingly, the rats were then euthanized and their liver tissue was transferred to the pathology lab in 10% formalin. Samples were examined by conventional histopathological techniques using the Hematoxylin & Eosin, and Perls’ Prussian blue staining methods, and observed under the optical microscope. Results: The findings showed that nano-iron oxide and iron oxide can lead to inflammation in hepatic lobules and portal triads, sinusoidal dilatation, abnormal proliferation of the hepatocytes and Kupffer cells, and some hepatocyte degeneration. Simultaneous quercetin treatment was found to reduce the histopathological effects of metal particles, particularly iron oxide particles. Moreover, samples were tested for signs of bile retention, fibrosis and necrosis, but the results were negative. Conclusion: The present study confirmed the anti-inflammatory and protective effects of quercetin as an herbal antioxidant on hepatotoxicity induced by nano-iron oxide and iron oxide.