✧LPS by binding with TLR4 induced pro-inflammatory changes (elevated levels of TNF-α, IL-1β, IL-6), increased uterine MPO activity, and activated NF-κB in MEECs.✧Decreased the expressions of Nrf2 and HO-1.✧Dimethyl itaconate ameliorated LPS-induced endometritis via the TLR4/NF-κB/Nrf2/HO-1 signaling pathway followed by suppressed levels of pro-inflammatory cytokines and an enhancement of the antioxidant response (Elevated levels of Nrf2 and HO-1). The gene discussed is NFE2L2; the disease is endometritis.