Lead is a toxic heavy metal with many recognized adverse health side effects. The central nervous system is the main target of lead toxicity. Although many studies on lead toxicity were conducted, the mechanism of lead toxicity remains uncertain. One possible attribution is the immature blood-brain barrier that causes lead exposure in children. Few studies have investigated the cytokine changes caused by this exposure. Novel cytokines were detected by RayBio(®) Human Cytokine Antibody Array and validated by enzyme-linked immunosorbent assay. Several children were admitted to West China Second University Hospital, after a serious lead pollution event in longchang, Sichuan, China. A total of 4 children with elevated blood lead levels (BLLs) and 4 children with low BLLs were randomly chosen in the discovery set, and 40 children with elevated BLLs and 40 children with low BLLs were included in the validation set. Leptin and interleukin-8 (IL-8) were identified to be significantly different between children with elevated and low BLLs via RayBio(®) Human Cytokine Antibody Array. In the validation set, IL-8 was higher in children with elevated BLLs [median(P25-P75), 117.69(52.31-233.63) pg/mL] than in children with low BLLs [median(P25-P75): 17.70(10.75-26.52) pg/mL] (p=0.000). Leptin was lower in children with elevated BLLs [median(P25-P75): 1658.23(1421.86-2606.55) pg/mL] than in children with low BLLs [median(P25-P75): 4168.68(3246.32-4744.94) pg/mL] (p=0.000). In children with low BLLs, leptin was higher in children with BLLs<3 μg/dL (N=7) [median(P25-P75): 7220.86(4265.72-7555.15) pg/mL] than in children with BLL ≥ 3 μg/dL (N=33) [median(P25-P75): 4103.86(3163.40-4678.34) pg/mL] (p=0.026); IL-8 was significantly different in children with BLL<4 μg/dL (N=13) [median(P25-P75): 12.49(8.25-14.86) pg/mL] than in children with BLL≥4 μg/dL (N=27) [median(P25-P75): 21.98(13.64-33.50) pg/mL] (p=0.013). The results defined specific changes in cytokine expressions to lead exposure, which can be used to explore the mechanism of lead toxicity and monitor lead exposure.