Recently, the use of nanomaterials in different biological and biochemical fields took an increased trend especially Iron oxide nanoparticles (IONPs) because of its physical, chemical and magnetic properties. Despite wide usage of IONPs, it has lethal side effects. This study was constructed to evaluate the harmful effects of IONPs on different organs of mammalian and avian models (Rattus norvegicus domestica) and (Columba livia domestica) respectively, and to assess the role of deferoxamine as an iron chelator for alleviation of IONPs-induced side effects. Both animal models were divided into six groups served as control, IONPs-treated for 1 hour or 1 week, deferoxamine (DFO)-treated for 1 week, IONPs/DFO-co-treated for 1 hour or 1 week. Atomic absorption spectrophotometric (AAS) analysis and biochemical analysis for hepatic and renal functions were performed after animal sacrifice. The AAS analysis showed that the iron levels almost increased significantly in the blood, liver, kidney and spleen after injection of the IONPs alone for 1 week compared to control. While the co-injection of IONPs and DFO for 1 week caused a significant decrease in iron levels compared to the IONPs alone. Concomitantly, the levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase and (AST) and levels of creatinine and uric acid showed a significant increase in the IONPs-treated animals compared to control groups. Whereas a significant decrease of ALT, AST, creatinine and uric acid in the animals treated with IONPs and DFO together compared to animals treated with IONPs alone.