Protocatechuic acid (PA), a major metabolite of anthocyanins, has been reported to possess antioxidant and anti-inflammatory activities. However, the effects of PA on LPS-induced inflammatory responses in microglia have not been reported. The aim of this study was to investigate the anti-inflammatory effects and molecular mechanisms of PA on LPS-stimulated BV2 microglia. The production of inflammatory mediators TNF-α, IL-6, IL-1β, and PGE2 were detected by ELISA. TLR4, NF-κB and MAPKs activation were detected by western blotting. Our results demonstrated that PA dose-dependently inhibited LPS-induced TNF-α, IL-6, IL-1β, and PGE2 production. In addition, PA suppressed LPS-induced TLR4 expression, NF-κB and MAPKs activation, which resulted in the inhibition of inflammatory mediators. In conclusion, these results suggested that PA exhibited anti-inflammatory effects on LPS-stimulated BV2 microglia and the mechanisms were involved in the inhibition of TLR4-mediated NF-κB and MAPKs signaling pathways.