Maintaining a low glucose concentration in airway surface liquid (ASL) is important for defence against infection. The Na+-coupled glucose cotransporter SGLT1 is present in the lung and may aid in removing glucose which diffuses across the epithelium into the ASL1. Metformin decreased glucose diffusion across airway in vitro2 and azithromycin is thought to have similar effects by increasing transepithelial electrical resistance3. Metformin has also been shown to alter ion transport processes across epithelia4. Thus, we tested the hypothesis that glucose concentration in ASL is modulated by inhibitors of SGLT1, metformin and azithromycin. Wistar rats were given terminal anaesthesia with intra-peritoneal (IP) injection of 0.5 ml Hypnorm/0.5 ml Hypnovel /1 ml water at a final dose of 2.7 ml.kg. The circulation to the lungs was isolated by cardiac bypass and perfused with a modified Ringer’s solution + 5mM glucose. The lung lumen was filled with the same solution (10ml.kg-1), without glucose, but with Blue Dextran (5mg.ml-1; an impermeant tracer to determine lung liquid absorption rate (Jv)). The SGLT inhibitor phloridzin (PZ) 100µM, was instilled into the lungs after a period of control sampling. Metformin (MET) 20mg was given IP on 2 consecutive days prior to the experiment, and azithromycin (AZ) 10mg.kg-1 was given IP for 1 day prior to the experiment. PZ increased glucose concentration in the lung lumen from 0.053 ± 0.008 mM to 0.362 ± 0.045 mM over a period of 70 minutes (P=0.01; n=6). There was no significant effect of treatment on final lung lumen glucose concentration, compared to vehicle control (0.298 ± 0.14 mM to 0.915 ± 0.29 mM; P=0.09; n=7) with MET (0.185 ± 0.09 mM to 0.663 ± 0.18 mM; P=0.59; n=3) or AZ (0.175 ± 0.09 mM to 0.7890 ± 0.23 mM; P 0.79; n=3) on the PZ induced change in glucose concentration. PZ decreased Jv from -0.024 ± 0.003 ml.min-1.dry lung weight -1 to -0.012 ± 0.003 ml.min-1.dry lung weight -1 (P=0.02; n=6) consistent with inhibition of SGLT1 mediated Na+ uptake which drives fluid absorption. Treatment with MET or AZ, produced the same effect as PZ alone. AZ -0.015 ± 0.001 ml.min-1.dry lung weight-1 (P=0.61; n=3); MET -0.016 ± 0.001 ml.min-1.dry lung weight -1 (P=0.13; n=3); AZ and MET vehicle control -0.009 ± 0.002 ml.min-1.dry lung weight -1 (P=0.43; n=7). In conclusion, transport via SGLT1 removes glucose that diffuses across the lung epithelium into the ASL and this process also contributes to lung fluid absorption. Thus SGLT1 maintains a low glucose concentration in ASL. There was no effect of metformin or azithromycin on glucose diffusion into ASL or on SGLT function using this treatment regimen.