The bran fractions of certain varieties of sorghum (Sorghum bicolor) grain are rich sources of phytochemicals and antioxidants. In this article, the anti-inflammatory actions of extracts of select sorghum brans were evaluated in two experimental inflammatory systems: (1) the release of cytokines by lipopolysaccharide-activated peripheral blood mononuclear cells and (2) 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema in mice. A 1:200 dilution of a 10% (wt/vol) ethanol extract of black sorghum bran significantly inhibited the secretion of the pro-inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha. Ethanolic extracts of both black and sumac varieties of sorghum bran significantly reduced edema in inflamed ears as measured by ear thickness and ear punch weight 6 hours following TPA application. The degree of inhibition was similar to that observed with indomethacin. Black sorghum bran significantly diminished the increase in myeloperoxidase activity 24 hours following the application of TPA. No anti-inflammatory activity was observed with white and Mycogen sorghum bran varieties or with oat, wheat, or rice brans in the mouse ear model. The anti-inflammatory activity observed with these brans correlated with their phenolic content and antioxidant activity. These results demonstrate that select sorghum bran varieties possess significant anti-inflammatory activity.