Carbon-based nanomaterials have important research significance in various disciplines, such as composite materials, nanoelectronic devices, biosensors, biological imaging, and drug delivery. Recently, the human and ecological risks associated with carbon-based nanomaterials have received increasing attention. However, the biological safety of carbon based nanomaterials has not been systematically studied. In this study, we used different types of carbon materials, namely, graphene oxide (GO), single-walled carbon nanotubes (SWCNTs), and multiwalled carbon nanotubes (MWCNTs), as models to observe their distribution and oxidative damage in vivo. The results of Histopathological and ultrastructural examinations indicated that the liver and lungs were the main accumulation targets of these nanomaterials. SR-μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu$$\\end{document}-XRF analysis revealed that SWCNTs and MWCNTs might be present in the brain. This shows that the three types of carbon-based nanomaterials could cross the gas–blood barrier and eventually reach the liver tissue. In addition, SWCNTs and MWCNTs could cross the blood–brain barrier and accumulate in the cerebral cortex. The increase in ROS and MDA levels and the decrease in GSH, SOD, and CAT levels indicated that the three types of nanomaterials might cause oxidative stress in the liver. This suggests that direct instillation of these carbon-based nanomaterials into rats could induce ROS generation. In addition, iron (Fe) contaminants in these nanomaterials were a definite source of free radicals. However, these nanomaterials did not cause obvious damage to the rat brain tissue. The deposition of selenoprotein in the rat brain was found to be related to oxidative stress and Fe deficiency. This information may support the development of secure and reasonable applications of the studied carbon-based nanomaterials.