Although adverse health effects of particulate matter with a diameter of < 100 nm (nanoparticles) have been proposed, biological evidence supporting their promotion of the inflammatory lung response in vivo is limited. This study investigated the impact of pulmonary exposure to carbon black nanoparticles (CBNP) on emphysematous lung injury induced by porcine pancreatic elastase (PPE) in mice. Vehicle, two sizes (14 and 56 nm) of CBNP (50 mu g/body: 4 mg/kg), PPE (0.03 U/body: 1 U/kg) or PPE + CBNP was administered intratracheally; thereafter, parameters of inflammatory lung changes were evaluated at several time-points. CBNP of 14 nm significantly induced acute lung inflammation in non-elicited subjects and aggravated PPE-elicited airway neutrophilic inflammation at an early stage (day 1), which was concomitant with the enhanced lung expression of pro-inflammatory cytokines such as interleukin-1 beta and chemokine such as keratinocyte-derived chemoattractant. Further, 14-nm CBNP exaggerated emphysematous lung structural changes at a delayed stage (day 14). On the other hand, 56-nm CBNP induced lung inflammation but did not influence PPE-elicited pathophysiology in the lung. Taken together, CBNP at an optimal size and dose can exacerbate PPE-induced pulmonary inflammation and emphysema. This enhancement may be mediated, at least partly, via the increased local expression of pro-inflammatory molecules.