Environmental estrogens, such as bisphenol A (BPA) that is normally used in the manufacture of food and beverage containers, pose increasingly worrisome hazards to human and wildlife health. The adverse effects of BPA are multifaceted; while close attention has been paid to their effect on the immune response system, especially the possible etiology of asthma in children and adults. The underlined mechanism of how BPA influences the biological pathways to alter the normal immune response system is unknown. Here, we report to use various proteomics and biological experiments to identify BPA-targeting proteins and protein pathways in human cell lines and mouse CD4+T cells. The outcomes of these experiments revealed that the cellular respiration, phagosome maturation and especially the Sirtuin signaling pathways are among the top canonic or KEGG pathways perturbed by BPA.