Corn silk (CS) has long been consumed as a traditional herb inKorea. Maysin is a major flavonoid of CS. The effects ofmaysin on macrophage activation were evaluated, using themurine macrophage RAW 264.7 cells. Maysin was isolatedfrom CS by methanol extraction, and preparative C18 reversephase column chromatography. Maysin was nontoxic up to100 μg/ml, and dose-dependently increased TNF-α secretionand iNOS production by 11.2- and 4.2-fold, respectively,compared to untreated control. The activation and subsequentnuclear translocation of NF-κB was substantially enhancedupon treatment with maysin (1-100 μg/ml). Maysin alsostimulated the phosphorylation of Akt and MAPKs (ERK, JNK). These results indicated that maysin activates macrophages tosecrete TNF-α and induce iNOS expression, via the activationof the Akt, NF-κB and MAPKs signaling pathways. Theseresults suggest for the first time that maysin can be a newimmunomodulator, enhancing the early innate immunity.