This study reveals how artemisinin (ART) alleviates inflammation and ferroptosis in mastitis by activating the ZDHHC12/Nrf2/HO-1 axis.Researchers demonstrate that ART reduces iron accumulation, lipid peroxidation, and oxidative stress in Staphylococcus aureus-induced mastitis models.Mechanistically, ART upregulates ZDHHC12, promoting Nrf2 palmitoylation and nuclear translocation, which enhances HO-1 signaling.This pathway suppresses both inflammation and ferroptosis, offering a potential therapeutic strategy for mastitis.The findings highlight ART's dual role in modulating cellular defense mechanisms, providing new insights into its anti-inflammatory properties.The study underscores the importance of targeting ferroptosis and inflammation simultaneously for effective mastitis treatment.