Dietary components in combination may act synergistically and produce enhanced biological activities. Herein, we investigated the anti-inflammatory effects of 2 flavonoids, that is luteolin (LUT) and tangeretin (TAN) in combination. Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were treated with noncytotoxic concentrations of LUT, TAN, and their combinations. The results showed that LUT/TAN in combination produced synergistic inhibitory effects on LPS-stimulated production of nitric oxide (NO). ELISA results demonstrated that LUT/TAN in combination caused stronger suppression on the LPS-induced overexpression of proinflammatory mediators, such as prostaglandin E2 (PGE2 ), interleukin (IL)-1β, and IL-6 than LUT or TAN alone. Immunoblotting and Real-Time PCR analyses showed that LUT/TAN combination significantly decreased LPS-induced protein and mRNA expression of inducible nitric oxide synthase and cyclooxygenase-2. These inhibitory effects of the combination treatment were stronger than those produced by LUT or TAN alone. Overall, our results demonstrated for the first time that combination of LUT and TAN produced synergistic anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages.