Exposure　to　airborne　particulate　matter　(PM2.5)　is　associated　with　cardiovascular　diseases.　In　order　to　investigate　the　molecular　mechanisms　of　air　pollution-induced　CVDs　toxicity,　human　umbilical　vein　endothelial　cells　(HUVECs)　were　exposed　to　PM2.5　collected　from　January,　2016　winter　in　Beijing,　China.　We　performed　RNA　sequencing　to　elucidate　key　molecular　mechanism　of　PM　2.5-mediated　toxicity　in　HUVECs.　A　total　of　1753　genes,　864　up-regulated　and　889　down-regulated,　were　observed　to　be　differentially　expressed　genes　(DEGs).　Among　these,　genes　involved　in　metabolic　response,　oxidative　stress,　inflammatory　response,　and　vascular　dysfunction　were　significantly　differentially　expressed　(log2　FC　＞　4).　The　results　were　validated　by　quantitative　real-time　PCR　(qPCR)　and　Western　blot　for　CYP1B1,　HMOX1,　IL8,　and　GJA4.　Pathway　analysis　revealed　that　DEGs　were　involved　in　the　biological　processes　related　to　metabolism,　inflammation,　and　host　defense　against　environmental　insults.　This　research　is　providing　a　further　understanding　of　the　mechanisms　underlying　PM2.5-induced　cardiovascular　diseases　(CVDs).