Carbon black nanoparticle (CBNP) applications in high doses have been shown to be harmful to the lung. It is postulated that even small, environmentally relevant concentrations induce changes on lung homeostasis. The present study determined the impact of low-dose single and multiple CBNP (Printex 90) applications on mouse alveolar cell metabolism, especially inflammatory and oxidative stress parameters. Nanoparticles were administered to mice by a single or 8 oropharyngeal aspirations at wk 1, 2, 3, 5, 7, 9, 11, and 12 using 7 μg Printex 90, 7 μg DQ12 quartz (positive control), with water vehicle and saline as negative controls. After 2 d or 3 mo lung function was analyzed. Further lung histology, bronchoalveolar lavage fluid (BALF) parameters, and mRNA expression of cytokines and antioxidants enzymes in type II pneumocytes were measured on d 3 or after 3 mo. Single low-dose Printex 90 application induced no marked alterations in lung functions or BALF phospholipid levels but significant decrease in superoxide dismutase 2 and numerically elevated glutathione peroxidase 3 mRNA expression levels in type II pneumocytes. Multiple CBNP applications produced reduced lung function, collagen accumulation, elevated phospholipid levels in BALF, and a massive infiltration of macrophages. Type II pneumocyte mRNA expression of antioxidative enzymes remained unchanged throughout the subchronic experiment, but showed a significant decrease in interleukin (IL)-6Rα mRNA expression. This study demonstrates that an environmentally relevant CBNP concentration induced an acute inflammatory response, an effect that is exacerbated throughout the subchronic duration.