The aim of this study was to investigate the local pharmacokinetics and site-specific target efficiency of ambroxol hydrochloride (AH) dry powder inhalation (DPI) by comparing lung epithelial lining fluid (ELF) and plasma AH levels after tracheal administration (TA) with those after intravenous administration. Twelve rats were divided into two groups, one of which was given AH DPI (20 mg/kg) via the trachea and the other was given the same dose AH by intravenous injection (i.v.). Afterwards, each group was subdivided into two groups. The concentration of AH in the ELF was determined by microdialysis in one group while the concentration of AH in plasma was determined in the other group. After AH DPI (20 mg/kg) was given via the trachea, AH achieved a high local concentration in ELF and reached a C(max) at 1.5 h in plasma. After the same dose AH was given by i.v., AH reached a C(max) in ELF at 1.25 h. The (AUC(0-t))(ELF)/(AUC(0-t))(plasma) ratio (1.05-2.25) after TA differed significantly from the ratio (0.029-0.039) observed after intravenous administration (p < 0.05). All these results indicate that AH DPI can be delivered to a specific targeted site and achieve high target efficiency in ELF. DPI could be a useful drug delivery system for AH therapy of pulmonary diseases.