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In this study, the effects of inhaled surface\u2010coated nanoTiO<jats:sub>2<\/jats:sub> on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL\/6BomTac mice were exposed for 1 hr daily to 42.4 \u00b1 2.9 (SEM) mg surface\u2010coated nanoTiO<jats:sub>2<\/jats:sub>\/m<jats:sup>3<\/jats:sup> for 11 consecutive days by inhalation and were sacrificed 5 days following the last exposure. Physicochemical properties of the particles were determined. Pulmonary response to nanoTiO<jats:sub>2<\/jats:sub> was characterized using DNA microarrays and pathway\u2010specific PCR arrays and related to data on pulmonary inflammation from bronchial lavages. NanoTiO<jats:sub>2<\/jats:sub> exposure resulted in increased levels of mRNA for acute phase markers <jats:italic>serum amyloid A\u20101 (Saa1)<\/jats:italic> and <jats:italic>serum amyloid A\u20103 (Saa3<\/jats:italic>), several C\u2010X\u2010C and C\u2010C motif chemokines, and cytokine <jats:italic>tumor necrosis factor<\/jats:italic> genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more than 1.2\u2010fold (adjusted <jats:italic>P<\/jats:italic>\u2010value &lt; 0.05) following exposure. Real time polymerase chain reaction confirmed the upregulation of miR\u20101, miR\u2010449a and revealed dramatic induction of miR\u2010135b (60\u2010fold). Thus, inhalation of surface\u2010coated nanoTiO<jats:sub>2<\/jats:sub> results in changes in the expression of genes associated with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research. Environ. Mol. 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