Bioactivity-guided fractionation of the methanol extract from the leaves of Santolina insularis led to the isolation of one new xanthone, (E)-3-(6-[(E)-3-hydroxy-3-oxo-1-propenyl]-9-oxo-9H-xanthen-2-yl)-2-propenoic acid, together with six known flavonoids: hispidulin, nepetin, cirsimaritin, rhamnocitrin, luteolin and luteolin 7-O-beta-D-glucopyranoside. The structures were elucidated by means of 1D-, 2D-NMR spectroscopy and mass spectrometry. The topical anti-inflammatory activity of all isolated compounds and extracts was investigated employing the croton oil-induced dermatitis in mouse ear. The most active compound, luteolin, showed an ID50 of 0.3 micromol/cm(2) and prevented ear oedema more effectively than an equimolar dose of indomethacin within 24 h.