The cytotoxicity, apoptosis, reactive oxygen species (ROS) and DNA damage induced by the commercial diesel exhaust particulate matter (PM) (SRM2975) with concentrations ranging from 0.1 μg mL-1 to 20 μg mL-1 were assessed in human umbilical vein endothelial cells (HUVECs) in vitro. An epigenetics-wide investigation of DNA methylation profiles was also performed using a new methylation beadchip (Illumina 850 K) to identify the health effects of traffic-derived nanoparticulate matter (nPM) with a concentration of 20 μg mL-1. By characterising its physical and chemical properties, we found that SRM2975 is a highly disordered graphitic structure material with a nanometer dimension and a large surface area. Low levels of traffic-derived nPM (≤10 μg mL-1) induced cell apoptosis and DNA damage as well as increased intracellular ROS levels (p < 0.001). The HUVECs showed a significantly decreased cell viability following their exposure to traffic-derived nPM with a concentration of 20 μg mL-1 (p < 0.001). A total of 149 significant differential methylated probes between the control and traffic-derived nPM treated-cells were identified, among which 86.6% were hypermethylated. A gene ontology (GO) enrichment analysis of differential methylated genes reported that the majority of the enriched GO terms were related to calcium ion and heart muscle, and further Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis indicated that the top three enriched pathways were involved in three common subtypes of cardiomyopathy. Overall, these results demonstrated that traffic-derived nPM could induce cytotoxic effects and demonstrate robust associations with cardiomyopathy though differential DNA methylation as well as the physiologic process of ROS, oxidative stress, inflammation, cell death and calcium ion channel.