Astaxanthin, a carotenoid without vitamin A activity, has shown anti-oxidant and anti-inflammatory activities; however, its molecular action and mechanism have not been elucidated. We examined in vitro and in vivo regulatory function of astaxanthin on production of nitric oxide (NO) and prostaglandin E2 (PGE2) as well as expression of inducible NO synthase (iNOS), cyclooxygenase-2, tumor necrosis factor-a (TNF-a), and interleukin-1b (IL-1b). Astaxanthin inhibited the expression or formation production of these pro-inflammatory mediators and cytokines in both lipopolysaccharide (LPS)-stimulated RAW264.7 cells and primary macrophages. Astaxanthin also suppressed the serum levels of NO, PGE2, TNF-a, and IL-1b in LPS-administrated mice, and inhibited NF-kB activation as well as iNOS promoter activity in RAW264.7 cells stimulated with LPS. This compound directly inhibited the intracellular accumulation of reactive oxygen species in LPS-stimulated RAW264.7 cells as well as H2O2-induced NF-kB activation and iNOS expression. Moreover, astaxanthin blocked nuclear translocation of NF-kB p65 subunit and IkBa degradation, which correlated with its inhibitory effect on IkB kinase (IKK) activity. These results suggest that astaxanthin, probably due to its antioxidant activity, inhibits the production of inflammatory mediators by blocking NF-kB activation and as a consequent suppression of IKK activity and IkB-a degradation.