The current study aimed to assess the ability of oral quercetin to treat iron overload and compare it with deferoxamine (DFO). Four groups (each of seven) of adult male New Zealand rabbits with six months of age used in the current study were treated as follows for 28 days: Group C: Animals were injected intraperitoneally (I/P) with normal saline every 72 hours + normal saline orally each day (negative control). T1, T2, and T3 groups were I/P injected with iron dextran (100 mg/kg) once every 72 hours. Additionally, T2 group animals were treated with quercetin (350 mg/kg) once per day for 28 days, and T3 group animals were injected with DFO (125 mg/kg) intramuscularly once per day for 28 days. After 24 hours since the last administration, animals were anesthetized and sacrificed, and blood samples were taken directly from the heart to obtain blood serum. The result showed a significant decrease in serum iron, total iron binding capacity (TIBC), and transferrin saturation percentage in the T2 and T3 groups compared with the T1 group, while, hemoglobin didn’t show any significant difference between the T1, T2, and T3 groups. T2 and T3 also showed a significant decrease in malonaldehyde (MDA) and a significant increase in glutathione peroxidase (GPX) concentrations compared with the T1 group. Conclusion: Quercetin has a stronger effect as an iron chelating agent due to its antioxidant properties than deferoxamine in iron-overloaded rabbits. These results suggest that quercetin could be effective in the treatment of iron overload in the clinic.Key words: Quercetin, Deferoxamine, Iron overload, Rabbits, ferritin, HB, TIBC