The aim of this study was to investigate the modulation of an asthmatic response by titanium dioxide (TiO₂) or gold (Au) nanoparticles (NPs) in a murine model of diisocyanate-induced asthma. On days 1 and 8, BALB/c mice received 0.3% toluene diisocyanate (TDI) or the vehicle acetone-olive oil (AOO) on the dorsum of both ears (20 μL). On day 14, the mice were oropharyngeally dosed with 40 μL of a NP suspension (0.4 mg·mL⁻¹ (∼0.8 mg·kg⁻¹) TiO₂ or Au). 1 day later (day 15), the mice received an oropharyngeal challenge with 0.01% TDI (20 μL). On day 16, airway hyperreactivity (AHR), bronchoalveolar lavage (BAL) cell and cytokine analysis, lung histology, and total serum immunoglobulin E were assessed. NP exposure in sensitised mice led to a two- (TiO₂) or three-fold (Au) increase in AHR, and a three- (TiO₂) or five-fold (Au) increase in BAL total cell counts, mainly comprising neutrophils and macrophages. The NPs taken up by BAL macrophages were identified by energy dispersive X-ray spectroscopy. Histological analysis revealed increased oedema, epithelial damage and inflammation. In conclusion, these results show that a low, intrapulmonary doses of TiO₂ or Au NPs can aggravate pulmonary inflammation and AHR in a mouse model of diisocyanate-induced asthma.