Previously, a synthetic biflavone having a C-C (6-6") linkage ([6,6"]biflavone, BF6-6) was shown to possess considerable anti-inflammatory activity. The present investigation was conducted to develop more active anti-inflammatory biflavonoids having unique mechanisms of action based on the BF6-6 molecule. For this purpose, 5,7-dihydroxy[6,6"]biflavone (G168) was synthesized using Suzuki-Miyaura C-C cross coupling reaction. The anti-inflammatory activities of G168 were then examined on lipopolysaccharide-treated RAW 264.7 cells, carrageenan-induced paw edema and acetic acid-induced writhing in mice. It was found that G168 showed much stronger inhibition against cyclooxygenase-2-mediated $PGE_2$ production than the original molecule, BF6-6. It also demonstrated inhibitory activity against inducible nitric oxide synthase (iNOS)-mediated NO production at least partly by the down-regulation of iNOS. Furthermore, G168, administered intraperitoneally at a dosage of 1-5 mg/kg, showed a potent in vivo anti-inflammatory activity on carrageenan-induced paw edema and analgesic activity on acetic acid-induced writhing in mice. Therefore, the newly synthesized biflavonoid, G168, may be used as a synthetic lead for new anti-inflammatory drug development.