PM2.5-induced inflammation have been demonstrated in the cellular and animal models, but few studies reported the associations of schoolchildren exposure to PM2.5 with their serum inflammatory biomarkers. Our goal was to examine whether serum inflammation was activated after children with long-term exposure to PM2.5 in an industrialized city of Taiwan. Schoolchildren (n = 183) between the ages of 6 and 12 years living in southern Taiwan were recruited to measure their serum inflammation including interferon-γ (IFN-γ), IFN-α2, interleukin 1b (IL-1b), IL-2, IL-6, IL-10, IL-13, IL-17, monocyte chemotactic protein (MCP)-1, and tumor necrosis factor (TNF-α). The subjects were sorted into three groups based on residential addresses in low-PM2.5, high-PM2.5, and traffic-related-air-pollution (TRAP)-PM2.5 areas on the basis of long-term PM2.5 pollution data from air monitoring sites collected over the past decade. Children living in the TRAP-PM2.5 areas had significantly higher TNF-α serum levels than those living in the low-PM2.5 areas. Although serum levels of MCP-1 in children exposed to low PM2.5 concentrations were lower than those in children exposure to high and TRAP PM2.5 levels, the differences were nonsignificant. Principal component (PC) analyses revealed a close association between serum MCP-1 and outdoor PM2.5 (Rotated PC2 (RPC2) and percentage of variance = 10.5%), whereas serum IFN-γ, IFN-α2, IL-1b, IL-2, IL-6, IL-10, IL-13, IL-17, and TNF-α were highly correlated (RPC1 and percentage of variance = 45.5%). Children's serum TNF-α was significantly linked to PM2.5 exposure scenarios (p = 0.031) by the test of the multivariate analysis (adjusted R 2 = 0.033, p = 0.039), but the other variables of age (p = 0.147) and gender (p = 0.291) were not statistically significant. In conclusion, serum TNF-α might be positively and significantly correlated with the longitudinal exposure of schoolchildren to PM2.5, especially among children living in TRAP-PM2.5 region.