The effect of tuna extracts on the production of nitric oxide (NO) and cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), was investigated. All extracts and fractions from tuna significantly reduced NO production induced by lipopolysaccharide (LPS). The acetone+methylene chloride (A+M) extract, n-hexane and 85% aqueous methanol (MeOH) fractions had stronger inhibitory effects among them. The 85% aqueous MeOH fraction at a 10-㎍ concentration significantly decreased LPS-induced IL-6 and TNF-α productions at 6 h of incubation. In the case of LPS-induced IFN-γ production, the 85% aqueous MeOH fraction at a 3-㎍ concentration showed significantly higher levels at 48 h of incubation. These results show that the 85% aqueous MeOH fraction inhibited the production of NO and pro-inflammatory cytokines (IL-6, TNF-α), suggesting that this fraction acts as a potent immunomodulator.