Adverse effects of environmental nanoparticles are emerged due to their escape from the macrophage surveillance and access to microcirculation. Endothelium acts as a physiological barrier lining up the vessel walls and controls the transfer of nanoparticles between the blood and interstitial space. Similarly, the blood brain barrier at the level of brain microcirculation is the major site of blood-nervous system exchange and constitutes the physical barrier. However, the loss of endothelial function and integrity may result in the uncontrolled passage of the nanoparticles. Despite of some adverse properties, nanosized materials continue to be used inevitably in daily life. However, their mechanism of action in the exposed organism and their potential toxic effects are still being investigated in order to take preventive measures to save the human health. Thus, this review focuses on the possible output of the interaction of endothelium with the nanomaterials and the significance of the barriers during the exposure to nanoparticles.