Numerous studies have proven that nano titanium dioxide (nano TiO₂) can accumulate in animal brains, where it damages the blood brain barrier (BBB); however, whether this process involves destruction of tight junction proteins in the mouse brain has not been adequately investigated. In this study, mice were exposed to nano TiO₂ for 30 consecutive days, and then we used transmission electron microscopy to observe the BBB ultrastructure and the Evans blue assay to evaluate the permeability of the BBB. Our data suggested that nano TiO₂ damaged the BBB ultrastructure and increased BBB permeability. Furthermore, we used immunofluorescence and Western blotting to examine the expression of key tight junction proteins, including Occludin, ZO-1, and Claudin-5 in the mouse brain. Our data showed that nano TiO₂ reduced Occludin, ZO-1 and Claudin-5 expression. Taken together, nano TiO₂-induced damage to the BBB structure and function may involve the destruction of key tight junction proteins.