Carbon nanotubes (CNT) are new members of carbon allotropes similar to fullerenes and graphite. Because of their unique electrical, mechanical and thermal properties, carbon nanotubes are being evaluated for novel applications in electronics, aerospace and computer industries. Our previous work has established that exposure of human broncho-epithelial cells (BEAS-2B) cells to CNT induced oxidative stress as evidenced by the formation of free radicals, accumulation of lipid peroxidation products, and depletion of antioxidants. This was accompanied by ultra-structural and morphological changes, enhanced cytotoxicity, and apoptosis. In the current study, we investigated pulmonary toxicity of CNT after pharyngeal aspiration by C57BL/6 mice. We found that CNT caused dose-dependent formation of granulomatous bronchointerstitial pneumonia, fibrosis, and decreased pulmonary function. Administration of carbon nanotubes to C57BL/6 mice also resulted in a dose-dependent augmentation of biomarkers of inflammation and depletion of lung antioxidants. Overall, our data suggest that exposure to CNT leads to pulmonary toxicity realized through synergized interactions of inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and fibrosis.