Houttuynia cordata Thunb. (HC) is a medicinal herb that generally used in traditional Chinese medicine for treat-ing allergic inﬂammation. The present study investigated the inhibitory effect of the volatile oil from HC Thunb. on animal models of inﬂammation and the production of inﬂammatory mediators in vivo and in vitro. In vivo, xylene-induced mouse ear edema, formaldehyde-induced paw edema and carrageenan-induced mice paw edema were signiﬁcantly decreased by HC volatile oil. HC volatile oil showed pronounced inhibition of prostaglandin (PG) E2 and malondialdehyde production in the edematous exudates. In vitro exposure of mouse resident peritoneal macrophages to 1, 10, 100 and 1000 mg/mL of HC volatile oil signiﬁcantly suppressed lipopolysaccharide (LPS)-stimulated production of NO and tumor necrosis factor-a (TNF-α) in a dose-dependent manner. Exposure to HC volatile oil had no effect on cell viability and systemic toxicity. Furthermore, HC volatile oil inhibited the production of NO and TNF-α by down-regulating LPS-stimulated iNOS and TNF-α mRNA expression. Western blot analysis showed that HC volatile oil attenuated LPS-stimulated synthesis of iNOS and TNF-α protein in the macrophages, in parallel. These ﬁndings add a novel aspect to the biological proﬁle of HC and clarify its anti-inﬂammatory mechanism.