Human exposure to airborne PM2.5 has been linked to an increased risk of respiratory and cardiovascular diseases, possibly via the activation of systemic inflammation. However, the associations between airborne PM2.5 and systemic inflammation in humans remain inconclusive. Traffic-related air pollutants (TRAPs) are the major source of PM2.5 in urban areas; the adverse health effect of PM2.5 from TRAPs is currently a critical issue of public concern. The present cross-sectional study examines the relationship between PM2.5 exposure and systemic inflammation in order to consider the health impacts of TRAP PM2.5 on urban traffic conductors. All study participants, viz., office-based police officers (the reference) and traffic conductors (the exposure), were requested to carry a personal sampler to determine individual PM2.5 exposure. An adenovirus-based NF-κB luciferase reporter assay was used to determine the proinflammatory activity in serum samples collected from the study participants. The blood proinflammatory activity was presented as tumor necrosis factor-α (TNFα) equivalence (TNFα-EQ), which was extrapolated from the sigmoidal semi-logarithmic dose-response curve of the NF-κB reporter assay by TNFα. The levels of both personal PM2.5 exposure and blood proinflammatory activity (TNFα-EQ) in the exposure group (traffic conductors) were significantly higher than in the reference group (office-based police officers) (p < 0.05). The present study reveals a positive and significant association between personal PM2.5 exposure levels and blood TNFα-EQ levels in a linear regression model of y = 0.511x – 3.062 (y = log TNFα-EQ and x = log PM2.5; R = 0.231 and p = 0.047); the results suggest that exposure to TRAP PM2.5 significantly contributes to increased systemic inflammation in humans. This research provides clear evidence that long-term occupational exposure to TRAPs causes adverse health impacts, i.e., inflammation, on traffic conductors.