A key aspect of the lung innate defence system is the ability of the epithelium to regulate the Airway Surface Liquid (ASL) volume. The ASL electrolyte composition, volume and height are tightly regulated by transepithelial ion and water transport. Regulation of ASL physiology is required for effective ciliary beat and muco-ciliary clearance in the proximal airways. The net transepithelial Na+ absorption and Cl- secretion are closely controlled to maintain an appropriate ASL layer on the bronchial airway surface through the activity, respectively, of the amiloride-sensitive epithelial sodium channel (ENaC) and the Cystic Fibrosis Transmembrane conductance Regulator. Lipoxin A4 (LXA₄) is an endogenous anti-inflammatory molecule produced from arachidonic acid that has been reported to be reduced in inflammatory Cystic Fibrosis (CF) lung¹. CF is a severe genetic disease caused by mutations in the CFTR gene, which result in a marked reduction in Cl- secretion and an increased Na+ absorption. This electrolyte imbalance alters the ASL homeostasis and leads to a dehydrated airway lumen. Dehydration limits mucociliary clearance and favours chronic bacterial infection and inflammation. One of the therapeutic avenues in CF is to restore the depleted ASL by correcting the ion transport defects. We have investigated the effect of LXA₄ on the ASL height in CF and non-CF cell lines, and the possible role of LXA₄ in inhibiting Na+ hyper-absorption. Materials and Methods: CF (CuFi-1) and non-CF (NuLi-1) cell lines were grown to confluency on semi-permeable filters in order to obtain a differentiated polarised epithelium showing high transepithelial resistance and loaded with fluorescent dye Calcein AM (5μM). Dextran solution containing the Texas Red fluorochrome was applied on the apical side of the epithelium in order to label the ASL compartment. Live cell ASL height was measured using a laser scanning confocal microscope. Results: The steady-state ASL height in the CF epithelium was reduced when compared to the normal non-CF epithelium. The addition of LXA₄ (1nM) for 15 minutes to the basolateral side significantly increased ASL height from 5±0.28 µm (n=18) to 15.25±1.18 µm (n=19) in CuFi cells and from 9±0.27 µm (n=19) to 14.26 ±0.67 µm (n=46) in NuLi cells. The effect of LXA₄ to increase ASL height in CuFi cells was observed to be sustained over time to a level of 9.23±0.56 µm (n=28) at 30 min, and 7.86±0.92 µm (n=10) at 45 minutes (n=9). These rapid and sustained effects of LXA₄ on ASL height were abolished by the lipoxin receptor antagonist, boc2 (10nM). Discussion: LXA₄ treatment resulted in an increased ASL height in a CF bronchial epithelium cell line and may provide a novel avenue in complementing existing therapy.