Abstract: To investigate the toxic effects of atmospheric PM_2.5 and its different fractions on the rat cardiac myocyte H9C2, and explore the key fractions causing toxic effects on the cardiovascular system, the prepared samples, including the original PM_2.5 particles (designated OPP_2.5), water-soluble particles in PM_2.5 (designated WPP_2.5), the fat-soluble particles in PM_2.5 (designated FPP_2.5) and the pure particulate fractions of PM_2.5 (designated PPP_2.5), were exposed to H9C2 cells at different concentrations. The MTS method was used to detect the cell viability at 6, 10, 24, 48 and 72 h post-treatment, and according to the detected results, a low PM concentration (10 μg/mL) was selected for the following experiments. Firstly, appropriate kits were used to detect the activities of lactate dehydrogenase and superoxide dismutase at 24 h post-treatment; secondly, ELISA and RT-qPCR were employed to detect the production of inflammatory cytokines IL-6 and TNF-α, and finally, AP-site counting was conducted to determine the level of intracellular DNA damage at 24 h post-treatment. The results demonstrated that the insoluble samples (OPP_2.5 and PPP_2.5) showed strong inhibitory effects toward cell growth, and the sample groups with particle concentrations of 50 μg/mL and above may have killed all H9C2 cells for exposure times of more than 24 h; while the soluble samples (WPP_2.5 and FPP_2.5) showed very weak and even no inhibitory effects toward cell growth, and only FPP_2.5 at 400 μg/mL showed inhibitory effects from 6 h to 72 h post-treatment; all samples caused damage to H9C2 cells to some extent and decreased the activities of intracellular LDH and SOD; in addition, OPP_2.5 and FPP_2.5 played an evident role in inducing inflammatory injury in H9C2 cells. A conclusion can be reached that the insoluble samples of atmospheric PM_2.5 showed significant lethal effects toward H9C2 cells, and OPP_2.5 showed the strongest and the most comprehensive toxic effects on H9C2 cells.