Exposure to airborne fine particulate matter (PM_2.5) is associated with various adverse effects. However, the molecular mechanism involved in PM_2.5-elicited energy metabolic reprogramming and the toxic chemical determinants within PM_2.5 are not well elucidated. In this study, nontargeted and targeted metabolomics research were conducted to investigate the overall metabolic changes and relevant toxicological pathways caused by Taiyuan winter total PM_2.5 and its water soluble and organic soluble fractions in human lung bronchial epithelial cells (BEAS-2B). The results showed that significant metabolome alterations in BEAS-2B cells were observed after the exposure of total PM_2.5 and its organic soluble fraction. Purine metabolism, arginine and proline metabolism, glutathione (GSH) metabolism, tricarboxylic acid (TCA) cycle and glycolysis were mainly affected. Along with a significant increase of reactive oxygen species (ROS), malondialdehyde (MDA), nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), obvious metabolic phenotype remodeling from oxidative phosphorylation to glycolysis was found in BEAS-2B cells treated with total PM_2.5 and its organic soluble fraction. Compared with water soluble fraction, organic soluble fraction was found to play the dominant role in PM_2.5 toxicity. Our study provided novel insights into the mechanism of PM_2.5-elicited toxicity.