This study provides evidence that estradiol induces the expression and secretion of antimicrobial peptide S100A7 in gMECs through the ERK1/2-signaling pathway, and lays a theoretical foundation for exploring the phenomenon that the incidence of clinical mastitis is highest during the dry period and perinatal period, and the role of estradiol in regulating the synthesis and secretion of S100A7 in gMECs. The gene discussed is MAPK3; the disease is mastitis.