Elsholtzia splendens Nakai has been used in North-East Asia as an ingredient of folk medicines for treating cough, headache and inflammation. The present investigation was carried out to establish its in vivo anti-inflammatory activity using several animal models of inflammation and pain. The 75% ethanol extract of the aerial part of E. splendens significantly inhibited mouse croton oil-induced, as well as arachidonic acid-induced, ear edema by oral administration (44.6% inhibition of croton oil-induced edema at 400 mg/kg). This plant material also showed significant inhibitory activity against the mouse ear edema induced by multiple treatment of phorbol ester for 3 days, which is an animal model of subchronic inflammation. In addition, E. splendens exhibited significant analgesic activity against mouse acetic acid-induced writhing (50% inhibition at 400 mg/kg), while indomethacin (5 mg/kg) demonstrated 95% inhibition. E. splendens (5-100 microg/mL) significantly inhibited PGE2 production by pre-induced cyclooxygenase-2 of lipopolysaccharide-treated RAW 264.7 cells, suggesting that cyclooxygenase-2 inhibition might be one of the cellular mechanisms of anti-inflammation.