Polygonum perfoliatum is commonly used in folk medicine to treat inflammatory disorders in China. Present studies on the anti-inflammation effect of quercetin-3-O-β-D-glucuronide-methyl ester from Polygonum perfoliatum was evaluated in vivo models of both acute inflammations such as xylene-induced ear edema, acetic acid-induced vascular permeability. Quercetin-3-O-β-D-glucuronide-methyl ester showed a significant dose-related inhibition in xylene-induced ear swelling and acid-induced vascular permeability in mice. These results demonstrate that quercetin-3-O-β-D-glucuronide-methyl ester possesses a potent anti-inflammatory function on acute inflammation. These results also support the claims of traditional Chinese medicine practitioners about the use of Polygonum perfoliatum in the treatment of inflammatory disease.