The present study investigated the size-dependent translocation pattern and biological fate of intranasally instilled nano- and submicron-sized Fe2O3 particles (40 nm and 280 nm) in the CNS. The particle translocation in different parts of brain at 4 h, 12 h, 24 h, 3 d, 7 d, and 30 d after intranasal instillation were quantified using ICP-MS method. A biexponential model (correlation coefficient r = 0.98-0.99) was satisfactory to describe the particokinetic translocation behavior of Fe2O3 nanoparticles in brain. We found a size-dependent translocation pattern and a time-dependent translocation mode for nano- and submicron-sized Fe2O3 nanoparticles in the olfactory bulb, which are most significant in toxic concerns of nanoparticles in the CNS. The TEM images showed particle-like substances of approximately 35-50 nm were located in the axons of olfactory neurons and in the mitochondria and lysosomes of hippocampus cells in the 40 nm-Fe2O3 exposed mice. The synchrotron-based near-edge X-ray absorption spectroscopy (XANES) was used to identify the chemical forms of the nanoparticles in brain. The XANES results indicate that the presence of chemical speciation of the Fe2O3 nanoparticle (-17%) and protein-complex like apotransferrin-Fe2O3 (-16%) in the olfactory bulb, implying that self-coating of Fe2O3 nanoparticles with transferrin occurred in brain. All the findings suggest size-sensitive manners of nano- and submicron-sized Fe2O3 particles in the brain; the smaller one possesses evident detention properties in the CNS versus the larger one.