There is a lack of evidence regarding the association of short-term exposure to fine particulate matter (PM_2.5) with renal function in children and its underlying mechanism. We included 105 children aged 4–13 years from a panel study conducted in Wuhan, China with up to 3 repeated visits across 3 seasons from October 9, 2017 to June 1, 2018. We measured personal real-time PM_2.5 exposure concentration continuously for 72 h preceding each round of health examinations that included serum creatinine and cytokines. Linear mixed-effects models were performed to estimate the effects of PM_2.5 on estimated glomerular filtration rate (eGFR) over various lag times, and a mediation analysis was applied for the role of cytokines in association between PM_2.5 and eGFR. Results showed that personal exposure to PM_2.5 was dose-responsive related to decreased eGFR within lag 2 days. The effect was the strongest at lag 0 day with estimation of −1.69% [95% confidence interval (CI): -2.27%, −1.10%] in eGFR by a 10-μg/m³ increase in PM_2.5, and reached peak at lag 3 h, then declined over time. Such inverse relationships were more evident among children aged 4–6 years, or boys or those who lived proximity to major roadways <300 m. Notably, eGFR still held on to decrease even when PM_2.5 was below Class II Chinese ambient air quality standard at lag 0 day. Moreover, the effect of PM_2.5 on eGFR was significantly reduced in children with high and medium levels of serum chemokine ligand 27 (CCL27), but not in those with low CCL27. Furthermore, CCL27 was positively relevant to PM_2.5, and mediated proportion of CCL27 ranged from 3.75% to 6.61% in relations between PM_2.5 and decreased eGFR over various lag times. In summary, short-term PM_2.5 exposure might be dose-responsive associated with reduced eGFR whereby a mechanism partly involving CCL27 among healthy children.