Corn silk (CS) has long been consumed as a traditional herb in Korea. Maysin is a major flavonoid of CS. The effects of maysin on macrophage activation were evaluated, using the murine macrophage RAW 264.7 cells. Maysin was isolated from CS by methanol extraction, and preparative $C_{18}$ reverse phase column chromatography. Maysin was nontoxic up to $100{mu}g/ml$, and dose-dependently increased TNF-${alpha}$ secretion and iNOS production by 11.2- and 4.2-fold, respectively, compared to untreated control. The activation and subsequent nuclear translocation of NF-${kappa}B$ was substantially enhanced upon treatment with maysin ($1-100{mu}g/ml$). Maysin also stimulated the phosphorylation of Akt and MAPKs (ERK, JNK). These results indicated that maysin activates macrophages to secrete TNF-${alpha}$ and induce iNOS expression, via the activation of the Akt, NF-${kappa}B$ and MAPKs signaling pathways. These results suggest for the first time that maysin can be a new immunomodulator, enhancing the early innate immunity.