Interest has developed in natural molecules due to their clinically proven effects on skin deseases. Flavanones display several biological activities, and recently have been the focus of studies due to their anti-inflammatory effect. To improve their pharmacological profile four flavanones (A, B, C and D), were synthesized by structural modification of one flavanone natural 1 (semi-systematic name: (2S)-5,7-dihydroxy-6-prenylflavanone) extracted from Eysenhardtia platycarpa. The hydroalcoholic flavanone solutions (FS) were assayed to investigated their anti-inflammatory effect on two in vivo cutaneous inflammation models. Materials and methods: the topical anti-inflammatory effect of FS were evaluated against models of 12-O-tetradecanoylphorbol acetate (TPA) induced mouse ear edema and arachidonic acid (AA) in rat ear edema. Results: The vinylogous cyclized derivative (flavanone D) caused edema inhibition in the TPA- induced models with an inhibition of 96.27 ± 1.93 %; equally effective and potent in inhibiting the mouse ear edema as Indometacine had been. In addition, the AA-induced increase in ear thickness was reduced the most by the topical application of modulated ether (flavanone B). Conclusions: The in vivo and histology results suggest that flavanones B and D are effective as a topical anti-inflammatory agents in inflammatory processes. Thus, this new compounds represents a promising agent for the management of skin diseases with an inflammatory component.