The epithelium lining the airways forms a resistive barrier that maintains low glucose concentration in the airway surface liquid (ASL). Increase in blood glucose elevates ASL glucose (1) increasing the risk of respiratory infection as a consequence of airway inflammation and loss of integrity of the epithelium. Lipoxin is a naturally occurring eicosanoid synthesised at sites of inflammation, low formation in the airway of cystic fibrosis and asthmatic patients could explain the persistent airway inflammation observed in this cohort (2,3). The aim of this study was to investigate the effect of Lipoxin (endogenous lipoxin isomer-LXA4) treatment on transepithelial electrical resistance (TEER) and glucose flux on human airway epithelial cells (H441). H441 epithelial cells were grown at air-liquid-interface for 7-14 days to form confluent polarised monolayers. Cells were treated with 100nM LXA4 on the apical surface or basolaterally in the medium or both (bilaterally) and compared to vehicle (ethanol) control. TEER of the monolayers was measured using an epithelial voltohmmeter over 72 hours. The effect of LXA4 on transepithelial glucose flux was assessed by measuring the paracellular diffusion of 14C-L-glucose (1µCi) plus 10mM D-glucose in Krebs added to the basolateral side of the transwells, with glucose free Krebs on the apical surface. The appearance of L-glucose was measured after 1 hour of incubation in apical and basolateral samples. Values are means ± S.E.M., compared by Student’s ttest. Bilateral LXA4 treatment after 24 hours significantly increased TEER from 95 ± 16 Ω.cm2 to 130 ± 17 Ω.cm2 (P=0.025; n=4)compared to vehicle control from 96 ± 22 Ω.cm2 to 107 ± 18 Ω.cm2. While apical LXA4 incubation TEER changed from 101 ± 36 Ω.cm2 to 113 ± 37 Ω.cm2 (P=0.51; n=3) was less effective and no change was found with basolateral treatment. This compares to previous research with 1mM Metformin added basolaterally for 18 hours increased TEER by 36 ± 14% Ω.cm2 (P<0.0001; n=15) and reduced glucose flux. With LXA4 an increase in TEER was inversely correlated with a decrease in glucose flux by 12 ± 3% (P=0.09; n=2), no significant difference was observed with apical incubation with LXA4. In conclusion we provide evidence that LXA4 could potentially reduce glucose flux by reducing transepithelial permeability in airway epithelial cells. This highlights a new possible therapeutic benefit of LXA4 in the prevention of lung infection.