This study evaluated the effects and potential mechanisms of Qufeng Xuanfei decoction in animal model of post-infectious cough. Sixty SD rats were randomly divided into six groups (10 animals per group): control, disease model, low- (4.62 g kg(-1)), medium- (9.24 g kg(-1)), and high-dose (13.86 g kg(-1)) decoction, and positive treatment groups (dextromethorphan hydrobromide, 8 mL kg(-1)). To model post-infectious cough, all but control group animals were challenged with exposure to 50 g sawdust and 10 cigarette smokes for 30 min day(-1) for a total of 10 days, followed by subsequent exposures to lipopolysaccharide (20 µg) and capsaicin (10(-4) M) aerosols. The drugs were given by oral gavage for 15 days after which lung pathology, cell counts and cell differentials in bronchoalveolar lavage (BAL), and concentrations of neuropeptides [substance P (SP), neurokinins A (NKA) and B (NKB), and calcitonin gene-related peptide (CGRP)] in BAL (ELISA) were assessed. Compared with control group animals, significant inflammation and damage to bronchial epithelium were observed in the disease model group. A marked decrease in BAL percentages of all types of inflammatory cells was observed in the decoction-treated groups, with most changes in the medium-dose decoction group (p < 0.001 vs. disease model group). Further, airway inflammation and damage, as well as the levels of SP, NKA, NKB, and CGRP in BAL decreased the most in the medium-dose group (p < 0.001 vs. disease model group). In conclusion, medium-dose Qufeng Xuanfei decoction efficiently decreases the levels of neuropeptides, attenuates airway inflammation, and promotes recovery from disease.