Human exposure to airborne PM2.5 has been linked to increased risk of respiratory and cardiovascular diseases, possibly via activation of systemic inflammation. However, associations between airborne PM2.5 and systemic inflammation in humans remained inconclusive. The 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 aimed to examine the relationship between PM2.5 exposure and systemic inflammation for considering health impacts of TRAP PM2.5 on urban traffic conductors. All study participants, i.e., office policemen (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 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 NF-κB reporter assay by TNFα. Levels of both personal PM2.5 exposure and blood proinflammatory activity (TNFα-EQ) in the exposure group (traffic conductors) were significantly higher than that in the reference group (office policemen) (p < 0.05). The present study revealed 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 result suggests that exposure to TRAP PM2.5 significantly contributes to the increased systemic inflammation in humans. The study provides clear evidence that long-term occupational exposure to TRAPs causes adverse health impacts, i.e., inflammation, on traffic conductors.