Citrus peel has been used as a Traditional medicine in Asia to treat coughs, asthma and bronchial disorders. Therefore, the anti-inflammatory effects of 3,5,6,7,3′,4′-hexamethoxyflavone (quercetogetin, QUE) isolated from Citrus unshiu peel were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. The results showed that QUE repressed the production of prostaglandin E2 and nitric oxide by suppressing LPS-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase. It also suppressed the production of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α cytokines, and decreased the nuclear translocation of NF-κB by interrupting the phosphorylation of NF-κB inhibitor α in macrophage cells. Based on the finding that QUE inhibited the phosphorylation of ERK protein expression in LPS-induced RAW264.7 cells, it was confirmed that inhibition of inflammatory responses by QUE was mediated via the ERK pathway. Therefore, this study suggests that QUE has strong anti-inflammatory effects, making it a promising compound for use as a therapeutic agent in treating inflammatory lung diseases, such as emphysema.