To improve biological activity of rupestonic acid, six rupestonic acid amide derivatives containing isoxazole were synthesized in the presence of DCC, HOBt/DMAP using the rupestonic acid and 3-aryl-5-isoxazole-methylamine as the starting materials. The synthesized compounds 3a similar to 3f were confirmed by the methods of H-1 NMR, C-13 NMR, IR, ESI-MS techniques and preliminarily assayed in vitro against influenza viruses A and B. The results showed that compound 3c showed better activity against both influenza viruses A (H3N2) and B, and compounds 3c and 3e had the higher inhibition against influenza B virus than the parent compound 1.