This study was conducted to determine the anti-inflammatory effect of Paeonia japonica extract. To investigate antioxidant effect, we performed scavenging activities on DPPH and ABTS radicals. It was found that the extracts (500 μg/mL) had 78.9% of DPPH free radical scavenging activity. And ABTS radical scavenging activity was 89.7% at 500 μg/mL. Also, Paeonia japonica extract significantly inhibited the production of TNF-α and IL-1β in LPSstimulated HaCaT cells. In addition, Paeonia japonica extract significantly inhibited the expression of COX-2, iNOS, MAPKs. These results show that Paeonia japonica extract have an anti-inflammatory effect. Therefore, this research suggests that Paeonia japonica extract may be a potential agent for ameliorating inflammation.