Sperminated dextrans (SD) having different average molecular weights (MWs; 10, 40 and 70 kDa) and numbers of amino groups were prepared as cationized polymers for use as absorption enhancers. The absorption enhancing effects on the pulmonary absorption of insulin in rats and the permeation of FITC-dextran (MW 4,400, FD4) through calu-3 cell (human airway epithelial cell) monolayers by SD were evaluated. SD significantly enhanced the pulmonary absorption of insulin SD and the permeation of FD4 through calu-3 cells. The enhancing effects on the absorption insulin and permeation of FD4 through calu-3 cells increased with an increase in the molecular weigh of SD over the range 10-70 kDa. SD may interact directly with the luminal surface of mucus membranes via an ion-ion interaction and then induce signals that open tight junctions resulting in intercellular permeation of water soluble drugs. SD may be useful as an absorption enhancer for pulmonary delivery of peptide and protein drugs.