Objective: To explore the mediation mechanism of coronary artery lesion among both male and female Kawasaki disease (KD) children. Methods: Children with KD that hospitalized in the Wenzhou Medical University affiliated Yuying Children’s Hospital from January 2009 to December 2014, were included in this study. Differences on demographical characteristics, clinical manifestations, laboratory indicators, regimen and time of treatment, results from pre/post echocardiography and treatment between male and female patients, were compared. The independent effect of gender on the risk of coronary artery lesions (CAL) was evaluated, and the mediating effect of BMI, visiting time and KD type on the association between gender and CAL were also studied. Results: The average BMI level of male patients was higher than that of female patients. The difference was statistically significant (P<0.001). The prevalence of overweight among male patients (20.9%) was higher than female (14.1%). The difference was statistically significant (P=0.011). Data from the multivariate logistic regression analysis confirmed that the incidence of CAL in male patients was higher than that in female patients (aOR=1.50, 95%CI: 1.06-2.12) but the CAL was mainly different before on the immunoglobulin therapy. Results from the mediation analysis showed that BMI was an important mediator in the association between gender and CAL, with the indirect effect as 1.05 (95%CI: 1.01- 1.10) and the proportion mediated as 13.0%. Conclusions Male patients presented higher incidence of CAL but was mainly reflected in the difference of CAL before the treatment. BMI was probably an important mediator related to the association between gender and CAL.