Folk medicine suggests that pomegranate (peels, seeds and leaves) has anti-inflammatory properties; however, the precise mechanisms by which this plant affects the inflammatory process remain unclear. Herein, we analyzed the anti-inflammatory properties of a hydroalcoholic extract prepared from pomegranate leaves using a rat model of lipopolysaccharide-induced acute peritonitis. Male Wistar rats were treated with either the hydroalcoholic extract, sodium diclofenac, or saline, and 1?h later received an intraperitoneal injection of lipopolysaccharides. Saline-injected animals (i.?p.) were used as controls. Animals were culled 4?h after peritonitis induction, and peritoneal lavage and peripheral blood samples were collected. Serum and peritoneal lavage levels of TNF-? as well as TNF-? mRNA expression in peritoneal lavage leukocytes were quantified. Total and differential leukocyte populations were analyzed in peritoneal lavage samples. Lipopolysaccharide-induced increases of both TNF-? mRNA and protein levels were diminished by treatment with either pomegranate leaf hydroalcoholic extract (57?% and 48?% mean reduction, respectively) or sodium diclofenac (41?% and 33?% reduction, respectively). Additionally, the numbers of peritoneal leukocytes, especially neutrophils, were markedly reduced in hydroalcoholic extract-treated rats with acute peritonitis. These results demonstrate that pomegranate leaf extract may be used as an anti-inflammatory drug which suppresses the levels of TNF-? in acute inflammation.