The leaves of Alchornea floribunda and Alchornea cordifolia are used traditionally as topical anti-inflammatory agents. Several studies have shown that the hexane extracts of the plant materials exhibited significant anti-inflammatory activity [1,2,3]. In the present study, we subjected the hexane extracts of Alchornea floribunda and Alchornea cordifolia leaves to column chromatographic separation and isolated two highly lipophilic fractions AFLF and ACLF respectively. The anti-inflammatory effects of these fractions were investigated using xylene – induced oedema as a model of inflammation. AFLF and ACLF at 5mg/ear showed significant (P<0.001) topical anti-inflammatory effect with oedema inhibitions of 64.0 and 79.0% at 2h respectively. These fractions showed significantly higher topical anti-inflammatory effect than 5mg/ear indomethacin (oedema inhibition of 48% at 2h). GC/MS analysis of these fractions revealed that AFLF is composed mainly of long chain saturated and unsaturated hydrocarbons (18.78%) and their oxygenated derivatives (1.89%), long chain carboxylic (fatty) acids (2.72%) and their esters (5.53%); while ACFL is rich in volatile oils euginol (21.26%) and cadinol (4.76%) and other constituents like long chain primary alcohols (4.78%), long chain saturated hydrocarbon, nanocosane (36.86) and steroid derivatives, ethyl iso-allocholate (4.59%) and 3-acetoxy-7,8-epoxylanostan-1-ol (15.86%). These constituents are highly lipophilic and can easily permeate lipoidal layers of skin. They may contribute significantly to the observed topical anti-inflammatory effect of Alchornea floribunda and Alchornea cordifolia leaf extracts.