Red ginger (Zingiber officinale var. Rubra) has been prescribed as an analgesic for arthritis pain in Indonesian traditional medicine. The surface color of the rhizome is purple because of the anthocyanidins in its peel. We prepared 40% ethanolic extract from dried red ginger (red ginger extract [RGE]) and evaluated its anti-inflammatory activity using acute and chronic inflammation models. In an acetic acid-induced mouse writhing model, RGE (10-100 mg/kg) suppressed both the frequency of writhing and the increase in permeability of abdominal capillaries. On the other hand, continuous treatment with RGE (10 mg/kg) significantly (P < .05) suppressed footpad edema in a rat adjuvant arthritis model. To clarify the anti-inflammatory mechanism of RGE, we examined the effect on prostaglandin (PG) and nitric oxide (NO) production from mouse leukemic monocytes (RAW264 cells) stimulated by lipopolysaccharide. RGE (3 and 10 microg/mL) significantly (P < .05) suppressed PGE(2) production, while it also suppressed NO production at 100 microg/mL. After bioassay-guided separation of RGE, we found that [6]-shogaol and gingerdiols suppressed NO production. Red dye fractions presumed to be proanthocyanidins also suppressed NO production at 100 microg/mL. Consequently, we found a potent suppressive effect of RGE on acute and chronic inflammation, and inhibition of macrophage activation seems to be involved in this anti-inflammatory effect. [6]-Shogaol, gingerdiols, and proanthocyanidins were identified as constituents that inhibited NO production.