Chronic obstructive pulmonary disease (COPD) is one of the main health problems worldwide. It is characterised by chronic inflammation in the lungs that leads to progressive, chronic, largely irreversible airflow obstruction. The use of long-acting β agonists remain today the frontline treatment for COPD with the aim of minimizing side effects and enhancing therapeutic usefulness. To this purpose, in this paper, mucoadhesive solid lipid microparticles (SLMs) containing a long-acting β-2 agonist, Salmeterol Xinafoate (SX) were prepared, characterised (size, z-potential, aerodynamic diameter, turbidimetric evaluations, drug loading and entrapping efficiency) and tested in a model of bronchial epithelial cells. It was demonstrated that the incorporation of SX into SLMs led to the production of particles suitable for inhalation and more efficient than the free molecule at increasing the cAMP expression in bronchial epithelial cells. In conclusion, the prepared systems, due to their aerodynamic behaviour and mucoadhesive properties, could improve the retention time of SX in the lung epithelium and its therapeutic effect, thus representing a good strategy for the treatment of COPD patients.