Ferric oxide (Fe₂O₃) nanoparticles are of considerable interest for application in nanotechnology related fields. However, as iron being a highly redox-active transition metal, the safety of iron nanomaterials need to be further studied. In this study, the size, dose and time dependent of Fe₂O₃ nanoparticle on pulmonary and coagulation system have been studied after intratracheal instillation. The Fe₂O₃ nanoparticles with mean diameters of 22 and 280 nm, respectively, were intratracheally instilled to male Sprague Dawley rats at low (0.8 mg/kg bw) and high (20 mg/kg bw) doses. The toxic effects were monitored in the post-instilled 1, 7 and 30 days. Our results showed that the Fe₂O₃ nanoparticle exposure could induce oxidative stress in lung. Alveolar macrophage (AM) over-loading of phagocytosed nanoparticle by high dose treatment had occurred, while the non-phagocytosed particles were found entering into alveolar epithelial in day 1 after exposure. Several inflammatory reactions including inflammatory and immune cells increase, clinical pathological changes: follicular hyperplasia, protein effusion, pulmonary capillary vessel hyperaemia and alveolar lipoproteinosis in lung were observed. The sustain burden of particles in AM and epithelium cells has caused lung emphysema and pro-sign of lung fibrosis. At the post-instilled day 30, the typical coagulation parameters, prothrombin time (PT) and activated partial thromboplastin time (APTT) in blood of low dose 22 nm-Fe₂O₃ treated rats were significantly longer than the controls. We concluded that both of the two-sized Fe₂O₃ particle intratracheal exposure could induce lung injury. Comparing with the submicron-sized Fe₂O₃ particle, the nano-sized Fe₂O₃ particle may increase microvascular permeability and cell lysis in lung epitheliums and disturb blood coagulation parameters significantly.