Lead (Pb) has adverse effects on our nervous system and renal systems. Young children are more vulnerable to Pb exposure. However, the role of low-level Pb exposure in the immune system and allergic diseases in children is not well established. The aims of this study are to investigate the associations between Pb exposure and allergic diseases; between Pb and immunoglobulin E (IgE) as an intervening variable; and gender-based differences. We used multistage stratified random sampling to recruit kindergarten children nationwide in Taiwan. Information about allergic diseases and environmental exposures was collected by questionnaire. We compared children with and without allergic diseases for blood Pb levels measured by inductively coupled plasma mass spectrometry. The association between blood Pb and allergic diseases was assessed by logistic regression and those between Pb and IgE by generalized linear models. We also conducted mediation analysis to evaluate how much risk of allergic diseases related to Pb exposure is explained by IgE. A total of 930 children completed specimen collections. There was a positive association between Pb and asthma. Blood Pb were also positively linked with serum IgE (β = 0.26 kU/l per ln-unit increase Pb concentration; 95% CI 0.009-0.50 kU/l), after adjusting for potential confounders. Analyses stratified by gender revealed that blood Pb correlated with IgE only in boys (β = 0.40 kU/l; 95% CI 0.03-0.76 kU/l). We estimated that 38% of the total effect of Pb exposure on asthma is mediated by IgE levels. In conclusion, Pb exposure is associated with both blood IgE and asthma in boys. Moreover, the effect of Pb exposure on asthma may be mediated by IgE levels.