Theaflavin-3,3'-digallate (TFDG) is a major polyphenol found in black tea with diverse biological activities. It has antioxidant activity, inhibiting the formation of superoxide radicals, singlet oxygen, hydrogen peroxide, and hydroxyl radicals in vitro (IC50s = 26.7, 0.83, 0.39, and 25.07 µmol/L, respectively). It also reduces hydroxyl radical-induced damage to plasmid DNA. TFDG (12.5-50 µM) prevents LPS-induced release of TNF-α, IL-1β, and IL-6, expression of JNK and p38, and nuclear translocation of NF-κB in RAW 264.7 cells. In vivo, TFDG reduces serum levels of TNF-α, IL-1β, and IL-6 and decreases pulmonary edema, pulmonary congestion, and thickening of the alveolar wall in a mouse model of LPS-induced acute lung injury. It also inhibits osteoclast formation, polarization, and osteoclastic bone resorption in vitro and reduces titanium particle-induced bone erosion and the number of mature osteoclasts in mice in a dose-dependent manner.