Objective The effect of the silica nanoparticles(SNs) on lungs injury in rats was investigated to evaluate the toxicity and possible mechanisms for SNs.Methods Male Wistar rats were instilled intratracheally with 1 mL of saline containing 6.25,12.5,and 25.0 mg of SNs or 25.0 mg of microscale SiO_2 particles suspensions for 30 d,were then sacrificed.Histopathological and ultrastructural change in lungs,and chemical components in the urine excretions were investigated by light microscope,TEM and EDS.MDA,NO and hydroxyproline(Hyp) in lung homogenates were quantified by spectrophotometry.Contents of TNF-α,TGF-β1,IL-1β,and MMP-2 in lung tissue were determined by immunohistochemistry staining.Results There is massive excretion of Si substance in urine.The SNs lead pulmonary lesions of rise in lung/body coefficients,lung inflammation,damaged alveoli,granuloma nodules formation,and collagen metabolized perturbation,and lung tissue damage is milder than those of microscale SiO_2 particles.The SNs also cause increase lipid peroxidation and high expression of cytokines.Conclusion The SNs result into pulmonary fibrosis by means of increase lipid peroxidation and high expression of cytokines.Milder effect of the SNs on pulmonary fibrosis comparing to microscale SiO_2 particles is contributed to its elimination from urine due to their ultrafine particle size. Objective The effect of the silica nanoparticles (SNs) on lungs injury in rats was investigated to evaluate the toxicity and possible mechanisms for SNs.Methods Male Wistar rats were instilled intratracheally with 1 mL of saline containing 6.25, 12.5, and 25.0 mg of SNs or 25.0 mg of microscale SiO 2 particles suspensions for 30 days, then then sacrificed. Histopathological and ultrastructural change in lungs, and chemical components in the urine excretions were investigated by light microscope, TEM and EDS. MDA, NO and hydroxyproline (Hyp) in lung homogenates were quantified by spectrophotometry. Factors of TNF-α, TGF-β1, IL-1β, and MMP-2 in lung tissue were determined by immunohistochemistry staining. Results there is massive excretion of Si substance in urine. in lung / body coefficients, lung inflammation, damaged alveoli, granuloma nodules formation, and collagen metabolized perturbation, and lung tissue damage is milder than those of microscale SiO 2 particles. Th e SNs also cause increase in lipid peroxidation and high expression of cytokines. Confluence The SNs result into pulmonary fibrosis by means of increasing lipid peroxidation and high expression of cytokines. Milder effect of the SNs on pulmonary fibrosis comparing to microscale SiO 2 particles contributed to its elimination from urine due to their ultrafine particle size.