Inorganic nanoparticles have been widely applied to various industrial fields and biological applications. However, the question as to whether nanoparticles are more efficiently absorbed into the systemic circulation than bulk-sized materials remains to be unclear. In the present study, the physico-chemical and dissolution properties of the most extensively developed inorganic nanoparticles, such as silica (SiO2), titanium dioxide (TiO2), and zinc oxide (ZnO), were analyzed, as compared with bulk-sized particles. Furthermore, the bioavailability of nanoparticles versus their bulk counterparts was evaluated in rats after a single oral administration and intravenous injection, respectively. The results demonstrated that all bulk materials had slightly higher crystallinity than nanoparticles, however, their dissolution properties were not affected by particle size. No significant difference in oral absorption and bioavailability of both SiO2 and TiO2 was found between nano- and bulk-sized materials, while bulk ZnO particles were more bioavailable in the body than ZnO nanoparticles. These finding will provide critical information to apply nanoparticles with high efficiency as well as to predict their toxicity potential.