Platycodin D (PLD), a triterpenoid saponin derived from the root of Platycodon grandiflorum, has been reported to possess anti-inflammatory activity. However, the protective effect of PLD on mastitis has not been reported. In the present study, we aim to investigate the anti-inflammatory feature of PLD on the primary bovine mammary epithelial cells (bMEC) challenged with LPS. The cell viability of bMEC was measured by MTT assay. The quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the gene expression of pro-inflammatory cytokines and western blotting was carried out to measure the expression of LXRα and NF-κB. The results showed that PLD inhibited LPS-induced TNF-α, IL-1β, and IL-6 expression in LPS-stimulated bEMC. Meanwhile, PLD suppressed LPS-induced NF-κB activation. Furthermore, PLD was found to up-regulate the expression of LXRα. The inhibition of PLD on NF-κB activation and inflammatory cytokines production were reversed by GGPP, the inhibitor of LXRα. In conclusion, our results suggested that PLD inhibited LPS-induced inflammatory response in bMEC by activating LXRα. PLD may be a potential therapeutic drug for mastitis.