Abstract <p>The unique physical, chemical and magnetic properties of ironoxide nanoparticles (INPs) open up wide prospects for the use ofnanomaterials in the diagnosis and therapy of various diseases.Despite the high interest from the scientific community, the mechanismof the effect of INPs on the physiology of living organisms hasnot been fully investigated. This is not least due to the fact thatthe toxicity of nanoparticles depends on multiple factors, includingtheir size, method of synthesis, and the presence of a shell. Thiswork was aimed to study the effect of synthetic and biogenic ferrihydriteINPs on the mouse kidney morphology, depending on the method oftheir synthesis and the presence of a polysaccharide shell afteroral administration. The animals (<i>n</i> =55) were allocated into 3 groups: group 1 (<i>n</i> =15)—control mice, fed food without INP supplementation; group 2(<i>n</i> = 20)—experimental mice,fed food supplemented with synthetic uncoated INPs; group 3 (<i>n</i> = 20)—experimental mice, fed food supplementedwith encapsulated biogenic INPs. The biological material (mousekidney) was sampled for standard histological examination a daybefore the onset of feeding with INP supplementation, as well as ondays 22 and 36 after that. It was found that long-term administrationof both synthetic and biogenic INPs was accompanied by hemodynamicdisorders in the kidney, as well as dystrophic and necrotic alterationsin renal parenchymal cells, leading to the development of renalfailure. Biogenic INPs displayed a highest reactivity, which isprobably due to the presence of a polysaccharide shell and the crystallinestructure of the ferrihydrite core.</p>