Synthesis of baicalein, oroxylin A and wogonin, major active constituents of Scutellaria baicalensis GEORGI, was successfully developed in a previous report. In this investigation of novel oroxylin A derivatives as potential anti-infl ammatory agents, a series of Mannich base derivatives at C-8 in A-ring of oroxylin A were designed and synthesized. All the oroxylin A derivatives exhibited signifi cant anti-infl ammatory activity against λ-carrageenan-induced rat hind paw edema (CIPE). The results showed that the target compounds, oroxylin A (4a) and derivatives 4b-i (oroxylin A bearings a 8-substituent as piperidin-1-ylmethyl, morpholin-4-ylmethyl, 4-methyl-piperazin-1-ylmethyl, 4-pyridin-2-yl-piperazin- 1-ylmethyl, 4-pyrimidin-2-yl-piperazin-1-ylmethyl, 4-(2-chloro-phenyl)-piperazin-1-ylmethyl, 4-(4-nitro-phenyl)- piperazin-1-ylmethyl, 4-(4-fluoro-phenyl)-piperazin-1-ylmethyl, respectively) exerted a remarkably anti-inflammatory effect with a signifi cant reduction in swelling. Among them, compounds 4b (8-morpholin-4-ylmethyl oroxylin A), 4c (8-piperidinyl-4-ylmethyl oroxylin A), and 4f (8-[N-(N-2-pyrimidinyl)-piperazin-1-yl]methyl oroxylin A) proved to be the most potent with over 100% inhibition at 20 mg/kg dose in the fi rst hour and potency lasted 5 hours in comparison to that of ibuprofen (as a positive control).