Neutrophil activation and migration during an inflammatory response is preceded or accompanied by plasma membrane electrical changes. Besides changes in calcium currents, neutrophils have a high permeability to potassium, mainly through potassium channels. However, the significance of potassium channels in neutrophil physiology is still unclear. Here, we show that the treatment of rats with the ATP-sensitive potassium channel blocker glibenclamide (4, 20, or 40 μmol/kg) dose dependently decreased carrageenan-,N-formyl-methionyl-leucyl-phenylalanine (fMLP)-, and lipopolysaccharide-induced neutrophil influx and fluid leakage into the interpleural space. On the other hand, minoxidil (an ATP-sensitive potassium channel opener; 25, 50, and 100 μmol/kg) increased both neutrophil influx and fluid leakage induced by a submaximal dose of carrageenan. In addition, in vitro human neutrophil chemotaxis induced by leukotriene B₄ or fMLP (both 1 μM) was fully blocked by glibenclamide (10, 30, and 100 μM) or tetraethylammonium (a nonselective potassium channel blocker; 1, 3, and 10 mM). Thus, our results disclose the possibility that ATP-sensitive potassium channels may have a role in neutrophil migration and chemotaxis and plasma exudation in the inflammatory response.