CFTR-/- and wild-type mice were infected with clinical strain of Pseudomonas aeruginosa and the action of RvD1 on airway inflammation, lung damage and bacterial count was assessed. Oral administration of RvD1 significantly reduced death, lung infection, neutrophil infiltration and histological signs of lung damage in both the mice models. Further, in murine lung macrophages sorted during Pseudomonas aeruginosa chronic infection, RvD1 regulated expression of toll-like receptors and microRNAs that lower the inflammatory signalling. These results unveil roles and mechanism of action of RvD1 in chronic Pseudomonas aeruginosa infection and give proof of concept for the therapeutic use of RvD1 to limit inflammation, promote resolution and potentiate microbial clearance in CF.