Objective: To explore the longitudinal association of the levels of plasma irisin among children with changes in obesity related parameters and newly onset obesity, and to explore whether physical activity (PA) and sedentary behavior(SB) have regulatory effects, to provide a scientific basis for the prevention and control of childhood obesity work. Methods: Cluster random sampling method was used to select 521 children from five schools in Guangzhou in 2017 at baseline and were followed up in 2019. A based on baseline PA and SB, children who meet the following criterion were selected:moderate vigorous intensity PA≥60 min/d or <150 min/week; and gender , age specific SB≥ P 75 or SB < P 25 . Plasma irisin concentration was measured in all the selected children. Multiple linear regression and Logistic regression were conducted to analyze the association. Results: The two year cumulative incidence of obesity, overweight and obesity, and central obesity was 2.82%, 6.57%, and 6.81%, respectively. There was no statistically significant association between plasma irisin levels and changes in obesity related parameters, newly onset overweight obesity or central obesity among children ( P >0.05). After stratified by PA, the irisin concentration in the low PA group was positively associated with weight change ( B=0.229, P =0.03). After stratified by SB, the irisin concentration in the low SB group was positively associated with the height change ( B=0.210, P <0.05). In addition, PA level and SB level both had a moderating effect on the association between plasma irisin levels and the weight change ( P PA=0.01, P SB =0.05). Conclusion PA and SB show moderating effect on plasma irisin concentration and weight gain. No association of irisin concentration with newly onset overweight or obesity among children has been found.