Caffeic acid possesses multiple biological effects, such as antibacterial, antioxidant, antiinflammatory, and anticancer growth; however, what effects it has on bovine mastitis have not been investigated. The aim of this study was to verify the antiinflammatory properties of caffeic acid on the inflammatory response of primary bovine mammary epithelial cells (bMEC) induced by lipopolysaccharide (LPS), and to clarify the possible underlying mechanism. Bovine mammary epithelial cells were treated with various concentrations (10, 50, 100, and 200 μg/mL) of LPS for 3, 6, 12, and 18 h; the results showed that LPS significantly inhibited cell viability in a time- and dose-dependent manner. When cells were treated with LPS (50 μg/mL) for 12h, the cell membrane permeability significantly increased, which promoted cell apoptosis. Various concentrations (10, 25, and 50 μg/mL) of caffeic acid could weaken the inflammation injury of bMEC induced by LPS without cytotoxicity. Proinflammatory cytokines (IL-8, IL-1β, IL-6, and tumor necrosis factor α) from bMEC were decreased. Nuclear transcription factor κB activity was weakened via blocking κB inhibitor α degradation and p65 phosphorylation. All these showed that the protective effect of caffeic acid on LPS-induced inflammation injury in bMEC was at least partly achieved by the decreased production of proinflammatory cytokines mediated by the effect of reducing the κB inhibitor α degradation and p65 phosphorylation in the nuclear transcription factor κB pathway. The use of caffeic acid would be beneficial in dairy cows during Escherichia coli mastitis as a safe and natural antiinflammatory drug.