Abstract Zinc oxide nanoparticles (ZnO-NPs) have antimicrobial and a number of other properties, rendering apt their use in biomedicine, environmental remediation, agriculture, and other fields. Given the potential use of these nanoparticles (NPs) in these areas, it is necessary to determine their toxic effects on biological systems. This work therefore analyzed the histological changes in the respiratory nasal epithelium of Mus musculus biomodels exposed to atmospheres containing ZnO-NPs at different concentrations (6, 15, and 40 mg/m 3 ). The NPs were synthesized using the Pechini polymeric complex method and characterized using techniques such as IR and Raman spectroscopies, X-ray diffraction (XRD), transmission (TEM), and scanning electron microscopy (SEM). The ZnO-NPs obtained had a wurtzite-type structure, with spheroidal morphology and a particle size of ~ 50 nm, and the Raman spectrum showed the presence of defects in its structure. The results of the treatments to which the biomodels were subjected showed that the inhalation of ZnO-NPs caused significant morphological changes in their nasal epithelium (squamous metaplasia and vascular congestion) and an acute inflammatory response when exposed to high concentrations of NPs (40 and 15 mg/m 3 ). Graphical Abstract