PM2.5 is a major public health concern and some severe diseases have been attributed to exposure to PM2.5. How-ever, a comprehensive understanding of gene and microRNA expression patterns induced by PM2.5 is missing. The objective of this study was to evaluate the toxicity of PM2.5 via genome-wide transcriptional analysis in the model teleost fish, zebrafish (Danio rerio). Gene ontology analysis revealed that the most impact gene functional categories induced by PM2.5 included oxidation-reduction process, transport, response to xenobiotic stimulus, response to chemical stimulus and metabolic process. Pathway and Signal-net analysis showed that the critical pathway involved in the response to exposure to PM2.5 was the metabolism of xenobiotics by cytochrome P450. Results from verification experiments also demonstrated that the key genes with degree higher than 10 induced by PM2.5 were related to metabolism of xenobiotics by cytochrome P450, including cyp3a65, mgst2, gstp1, gsto2, gsto1, cyp1a, ehX1, gsta1 and aldh3b1. The differential expression of 8 microRNAs corresponding to those in the human genome, revealed that PM2.5 could up-regulate let-7b, miR-153b-3p, miR-122, miR-24 and down-regulate ulet-7i, miR-19a-3p, miR-19b-3p and miR-7a, which suggested PM2.5 had multiple means through which it induced toxicity in living organisms, such as suppression of adaptive immune responses, autophagy, deregulation of metabolism, impaired vasorelaxation, progression of cancers, as well as hypertension, atherosclerosis and myocardial infarction. (C) 2017 Elsevier B.V. All rights reserved.