A series of pyridinone derivatives were synthesized and examined for inhibition of 5-lipoxgenase. The 6-substituted pyridinone derivatives(2a～2e) exhibited a prominent inhibitory activity on 5-lipoxygenase. Among them, 6-phenylthio-1-phenyl-2-methyl-3-hydroxy-4(1H)-pyridinone (2a) showed the most potent inhibitory activity (IC₅₀=2.52 μmol/L). As removal of substituent at 6- position of pyridinones, the inhibitory abilities of these compounds were almost vanished. The inhibition mechanism of pyridinone derivatives was discussed.