Iron oxide-silica nanoparticles (IOSi-NPs) were prepared from a mixture of ferrous chloride tetrahydrate and ferric chloride hexahydrate dropped into a silica xerogel composite. The structure and morphology of the synthesized maghemite nanoparticles into the silica xerogel were analysed by X-ray diffraction measurements, scanning electron microscopy equipped with an energy dispersive X-ray spectrometer, and transmission electron microscopy. The results of the EDAX analysis indicated that the embedded particles were iron oxide nanoparticles. The particle size of IOSi-NPs calculated from the XRD analysis was estimated at around 12.5 nm. The average size deduced from the particle size distribution is 13.7 ± 0.6 nm, which is in good agreement with XRD analysis. The biocompatibility of IOSi-NPs was assessed by cell viability and cytoskeleton analysis. Histopathology analysis was performed after 24 hours and 7 days, respectively, from the intratracheal instillation of a solution containing 0.5, 2.5, or 5 mg/kg IOSi-NPs. The pathological micrographs of lungs derived from rats collected after the intratracheal instillation with a solution containing 0.5 mg/kg and 2.5 mg/kg IOSi-NPs show that the lung has preserved the architecture of the control specimen with no significant differences. However, even at concentrations of 5 mg/kg, the effect of IOSi-NPS on the lungs was markedly reduced at 7 days posttreatment.