Objective To observe the efficacy of Xuanfei Mixture combined with western medicine in the treatment of acute exacerbation of chronic bronchitis, and its impact on serum levels of CXC chemokine receptor 4 (CXCR4), galectin-9 (Gal-9) and chemokine C-C motif ligand 3 (CCL3). Methods 96 patients with acute exacerbation of chronic bronchitis who were diagnosed and treated in our hospital from January 2020 to December 2021 were divided into an observation group (48 cases) and a control group (48 cases). The control group was treated with conventional western medicine, while the observation group was treated with Xuanfei Mixture on the basis of the control group. The efficacy and adverse reactions after treatment were compared between the two groups, the score of wheezing, expectoration and cough, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), maximal voluntary ventilation (MVV), CXCR4, Gal-9 and CCL3 levels were compared before and after treatment. Results The total effective rate was 95.83% in the observation group, which was significantly better than 79.17% in the control group (P<0.05). There was no significant difference in the adverse reaction rate between the two groups (P>0.05). There was no significant difference in the levels of wheezing, expectoration, cough score, FEV1, FVC, MVV, CXCR4, Gal-9 and CCL3 between the two groups before treatment (P>0.05). After treatment, the levels of wheezing, expectoration, cough score, CXCR4, Gal-9 and CCL3 in the two groups were significantly lower than those before treatment (P<0.01), and the levels of those in the observation group were significantly lower than those in the control group (P<0.01); while the levels of FEV1, FVC and MVV in the two groups were significantly increased compared with those before treatment (P<0.01), and the levels of those in the observation group were significantly increased compared with the control group (P<0.01). Conclusion Xuanfei Mixture can improve the efficacy of western medicine on acute exacerbation of chronic bronchitis, relieve symptoms and improve lung function, and its mechanism may be related to reducing the levels of CXCR4, Gal-9 and CCL3 in the body