Nanomaterials have been proposed as novel substrates for medical and commercial applications. However, such materials also may have novel toxicities, thus posing environmental and health concerns. We previously reported hepatic injury in mice following the intravenous administration of unmodified silica particles with diameters of 70 nm (SP70); this toxicity was not observed following administration by the same route of micro-size particles with diameters of 300 nm (SP300) or 1,000 nm (SP1000). In the present study, we used electron microscopy to investigate the dynamics of silica nanoparticles administered in mice. SP70 was observed in hepatocytes and in lung epithelial cells. Inclusion within hepatocytes was associated with accumulation of SP70 in the liver sinusoidal endothelial cells and passage through the space of Disse. In contrast, SP300 and SP1000 were not observed within the hepatocytes. To our knowledge, our report represents the first demonstration that silica nanoparticles accumulate in hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and lung tissue; accumulation of SP70 in liver sinusoidal endothelial cells correlated with the induction of liver injury.