Alpinetin has been reported to have anti-inflammatory effects. However, whether alpinetin has anti-inflammatory effects in LPS-induced endometritis has not been thoroughly elucidated to date. The aim of this study was to investigate the protective effects of alpinetin on LPS-induced endometritis in mice. A mouse model of endometritis was induced by LPS and alpinetin was given 1 h before LPS treatment. According to the results, alpinetin protected mice against LPS-induced endometritis by attenuating uterine histological changes and myeloperoxidase (MPO) activity. The LPS-induced inflammatory response was inhibited by alpinetin as confirmed by the inhibition of TNF-α, IL-1ß, and IL-6 production. Furthermore, LPS-induced TLR4 expression and NF-κB activation were significantly suppressed by alpinetin. In addition, the expression of PPAR-γ was dose-dependently increased by the treatment of alpinetin. Taken together, the results of this study showed that alpinetin had protective effects against LPS-induced endometritis in mice, and the beneficial effects were occurred through the activation of PPAR-γ and inhibition of the TLR4 signaling pathway.