Cystic fibrosis (CF) is a genetic disease caused by absence of the cystic fibrosis transmembrane conductance regulator (CFTR) affecting multiple organs. CFTR is an anion transporter that moves chloride and bicarbonate ions to the apical side of the airway epithelial surface. CFTR deficiency results in decreased airway surface liquid depth and abnormally acidic airway pH, leading to decreased mucociliary transport and subsequent airway infections with pathogens such as Pseudomonas aeruginosa. While a major anion transporter in the epithelium, CFTR is not the only channel responsibly for efflux of chloride to the apical surface of the airway. Additional chloride transporters such as TMEM16A, SLC26A9, and CLC2 are present on the airway and have been detected to be potential disease-modifying genes. Recently, these transporters have been postulated to be therapeutic targets for supportive therapies in CF and other airway diseases. Here, we sought to determine the role of these chloride transporters in the development of lung disease of the CFTR-/- rat model. Short-circuit current data suggest that the largest portion of chloride transport function in the rat lung is caused by CFTR; however there remains some residual non CFTR-dependent current that may be due to additional chloride transporters. To determine which were important in the airway, CFTR-/- rats at 1, 3, and 6 months of age were assayed for mRNA and protein concentrations of TMEM16A, SCL26A9, and CLC2 compared to their wild-type (WT) littermates. Tracheae from these rats were excised and mucus particles tracked to determine mucociliary transport. We also assayed rats before and after lung infection with P. aeruginosa. Initial results indicated that TMEM16A and SLC26A9 mRNA and protein expression are increased in CFTR-/- compared to their WT littermates at each age tested and remain elevated compared to control following infection with P. aeruginosa. CLC2 has increased expression in CFTR-/- rats only following infection with P. aeruginosa. We found no correlation between expression of these transporters and mucociliary transport rates. However, we believe that results obtained suggest that these transporters may be exploited via agonists to improve airway surface liquid depth and pH. Future studies will examine the role of these transporters in correction of CF airway pathophysiology.