Ceria nanoparticles (nanoceria) have been used as a fuel-borne catalyst, and are emitted in the particulate phase in the diesel exhaust. To evaluate the potential health risks of airborne nanoceria, the pulmonary and systemic consequences of nanoceria to ICR mice were studied under repeated transnasal instillation. Two different size nanoceria (7-nm and 25-nm) were chose, representing the nanoceria mostly used as fuel additives and the combustion products of the very nanoceria, respectively. As the first target organ of nanoceria, the lungs suffered serious damages manifested in the results of their biochemical and pathological examinations. The results demonstrated the penetration of nanoceria through air-blood barrier after the lung burden. Nanoceria were further transferred to the secondary target organs, mainly the liver and spleen. Nanoceria could also arrive at the central neural system via olfactory nerve pathway. The systemic accumulation of nanoceria finally triggered lipid peroxidation in multiple organs. Generally, the smaller nanoceria induced more severe pulmonary damage but similar systemic toxicity when compared with the larger one. These findings imply that using nanoceria as diesel fuel catalyst may cause health concerns. Additional studies are warranted to investigate the pulmonary and systemic health consequences of nanoceria additive to diesel fuel.