Aim: Cystic Fibrosis (CF) is the most frequent genetic disease in the Caucasian population. CF is caused by a defective gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation is DF508 which impairs functional CFTR expression in the apical plasma membrane due to trafficking defects of the CFTR protein. The aim of this investigation was to improve the CFTR channel function by inhibiting the cyclic guanosine mono phosphate (cGMP) degradation using the high-potency PDE5 blocker sildenafil. Methods: To verify if sildenafil corrects the trafficking defect of DF508 CFTR we quantified the amount of membrane inserted CFTR protein in the DF508 CFTR cell line CFBE41o- after incubation with 150-400mM sildenafil. The CFTR molecules in the plasma membrane were detected by Western blot analyses. Additionally, we determined CFTR molecules at the apical surface using immunofluorescence approaches. Furthermore, we determined whether Sildenafil is also able to enhance the activity of wildtyp CFTR. Therefore, we injected 200/400mM sildenafil into CFTR expressing Xenopus laevis oocytes. We analysed the changes in CFTR current, conductance and capacitance by CFTR channel activation using an IBMX/cAMP cocktail in TEVC measurements. Results: In CFBE41o- cells sildenafil leads to a dose dependent insertion of CFTR molecules into the plasma membrane. Interestingly, sildenafil increases the cAMP response also in wildtyp CFTR expressing oocytes. Conclusion: The PDE5 inhibitor sildenafil can restore trafficking of mutant DF508 CFTR protein to the cell membrane and may also stimulate normal CFTR activity in CFTR expressing Xenopus laevis oocytes. This leads to the assumption that sildenafil acts via 2 mechanisms but until now these mechanisms are not proven. Subsequently, these experiments indicate that sildenafil acts as a corrector just as well as a potentiator and therefore as a potent drug for the therapeutic treatment of cystic fibrosis.