The growing production and use of nickel (Ni) nanopowders with low biopersistence makes dissolution and accumulation degree in a body an important parameters needed for the risk assessment of nanoparticles. We propose an experimental approach for rapid determination of the dissolution degree of nanoscale (77 nm) and ultrafine (275 nm) Ni particles in synthetic biological solutions. It has been shown that after 2 h of exposure to simulating saliva and lysosomal liquid the dissolution degree of nanoparticles can reach 30 and 60 wt.%, respectively. With decreasing of the particle’s size, they are characterized by increased solubility in saliva and the pulmonary tract; and the particles completely dissolve in 24 h. There was an attempt to predict the potential extent of accumulation of nickel compounds in the human body with particles entering the body by saliva or with breathing: with 3.8 times size decrease the probability of nickel accumulation in a body can rise in 3.5 times.