The potential threat of superfine carbon black (CB) particles to human health has received attention, but there are few human toxicological data available. The purpose of this study was to investigate the relationships between serum CC16 and SP-A with small airway related pulmonary functions in CB workers. Ninety-nine male CB packers and 115 non-CB-exposed healthy male workers were recruited. Serum CC16 and/or SP-A and pulmonary function tests were evaluated, and the relationship between them were also analyzed. To further assess pulmonary damage induced by CB particles in target organs, an animal inhalation exposure study was conducted. Male C57BL/6 mice were exposed to 15 and 30 mg/m3 CB for 6 h per day for 28 days. Levels of CC16 and SP-A were evaluated by ELISA and immunohistochemical staining (IHC). The results showed a 20% decreased in median CC16 and a 15% increase in median SP-A among CB-exposed workers. FEV1%, FEV/FVC, MMEF%, FEF25%, and FEF75% were also decreased in CB-exposed workers (P < 0.05). A significant positive correlation was observed between serum CC16 concentration and FEV1/FVC, although a negative correlation was found between serum SP-A concentration and FEV1/FVC. Serum CC16 was significantly reduced by 72% in mice with high CB-exposure, and serum SPA was 1.65x and 1.17x higher than CB-unexposed control mice in low and high CB-exposed mice, respectively. Lung CC16 and serum CC16 levels were positively correlated in mice (P = 0.024). Long-term exposure to ultrafine CB particles is associated with a decrease in CC16 and an increase in SP-A in the peripheral blood of CB-exposed workers. In conclusion, superfine CB particles have the potential to cause small airway obstruction.