Abstract <p>Zinc oxide (ZnO) nanoparticles substantially (up to one million times in the number of particles per mass unit) differ in physical properties from their microsized chemical analog. Due to their smaller diameter (199 fold) and higher degree of sphericity (1.45 fold) compared with microparticles, nanoparticles are accumulated at a higher concentration (up to 1.45 fold) in the lungs, heart, and liver of rats upon repeated oral exposure to a total dose of 16 625 mg/kg of body weight over 24 days, which determines a higher degree of material accumulation. Increased bioaccumulation leads to the more pronounced (up to 2.29 fold compared with the effect of microparticles) development of oxidative stress, cytolysis, impaired thrombocytopoiesis, and the development of an inflammatory response and imbalance of neurotransmitters at the cellular and molecular levels. At the organ and tissue levels, pathomorphological necrotic changes develop in lung tissues (fibrinopurulent pneumonitis) and inflammatory disorders in bronchial tissues (panbronchitis) are more pronounced upon exposure to ZnO nanoparticles as opposed to the effect of microparticles. Disorders at the cellular, molecular, organ, and tissue levels confirm the more pronounced functional accumulation of ZnO nanoparticles compared with microparticles. The research results prove the more pronounced material and functional accumulation of ZnO nanoparticles compared with their microsized chemical analog. Application of the obtained results is aimed at increasing the effectiveness of the development of preventive measures including hygiene standards for the levels of concentration in environmental objects which are designed to provide health safety for workers who produce, as well as the general population who consume, products containing ZnO nanoparticles.</p>