The polysaccharide fucoidin, a homopolymer of sulfated L-fucose, is known, by interfering with the function of L-selectin, to inhibit leukocyte rolling, which is an early and essential step in the process of leukocyte extravasation into inflamed sites. We tested the inhibitory effect of fucoidin on neutrophil accumulation in lung inflammation induced by phorbol myristate acetate and peritoneal inflammation induced by thioglycollate in rabbits. Pretreatment (10 mg/kg) followed by continuous administration (10 mg/kg/h) of fucoidin dramatically reduced the number of neutrophils recruited into the lungs (determined by neutrophil counts in bronchoalveolar lavage fluid; 97.7 +/- 0.52% reduction) and peritoneal cavity (determined by neutrophil counts in peritoneal lavage fluid; 98.4 +/- 1.29% reduction). Fucoidin treatment also increased the systemic neutrophil count. These results suggest that the inhibition of leukocyte rolling, which may be a primary function of fucoidin, leads to a reduction of neutrophil accumulation at inflammatory sites, which may be beneficial for attenuating neutrophil-mediated tissue injury.