Inflammation has been forwarded as the key factor in the development of quartz-induced fibrosis and carcinogenesis and particle surface properties are argued as an important characteristic responsible for these pathological alterations. To evaluate the effect of surface modification on acute and subchronic inflammation, female Wistar rats were intratracheally instilled with 2 mg native quartz, or quartz coated either with polyvinyl-pyridine-N-oxide or with aluminium lactate. Various markers of lung toxicity, inflammation and oxidative stress were found to be enhanced at 3, 7, 21 and 90 days post-instillation of native quartz. Quartz-treated animals also showed enhanced immunostaining of Nuclear Factor kappa B (NFB) in alveolar macrophages and lung epithelium, as well as reduced IB levels in whole lung homogenate. Both surface modifications were found to inhibit most of the effects as observed with native quartz. NFB-activation was also observed in vitro in rat lung epithelial cells following treatment with lavage fluid from quartz-treated animals, as well as with conditioned medium of quartz-treated macrophages, and these effects appeared to be at least partly TNF-independent. In conclusion, the persistent subchronic inflammatory lung response following quartz exposure appears to be particle surface-driven and is associated with NFB-activation in both alveolar macrophages and the lung epithelium.