The nanotechnology has revolutionised the industry by significant economic and scientific impacts, applicable to various fields ranging from aerospace engineering, nano electronics to environmental remediation and medical healthcare. Nanotechnology has gained its momentum in nanomedicine because of therapeutic applications and diagnostic imaging. Health effects of nanomaterials are attracting considerable and increasing concern of the public and government worldwide. Vast usage of Fe2O3 NMs raised concerns about their unseen adverse effects. This study was undertaken to address the current deficient knowledge of oxidative stress responses of female wistar rats following 28days repeated oral exposure to Fe2O3 NMs. Characterization of Fe2O3 NMs revealed size, shape and charge of the NMs. Our results showed significant increase in lipid peroxidation with depletion in the reduced glutathione concentration in a dose dependent manner in liver and brain after treatment with Fe2O3 NMs. Proxidant enzymes catalase, glutathione reductase and glutathione s transferase were increased substantially in liver on treatment with high dose of Fe2O3 NMs. Superoxide dismutase was significantly decreased in liver. The altered antioxidant status indicates induction of oxidative stress in rat tissues. The results obtained emphasize the significance of toxicity assessments in evaluating the efficiency of Fe2O3 NMs for the safe implementation for medical applications.