Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory disease and eosinophils (EOS) participate in inflammation process. Acute exacerbation of COPD (AECOPD) is an inevitable trend in the development of the disease and has attracted widespread attention. In the present study, 108 hospitalized patients with AECOPD were collected and the levels of interleukin-13 and eosinophil cationic protein in the serum and sputum were measured to explore their clinical value in eosinophilic AECOPD patients. The patients were divided into an eosinophilic group (52 cases, 48.15%) and a noneosinophilic group (56 cases, 51.85%). The eosinophilic group had fewer acute exacerbations in the past year, shorter average hospitalization days, lower respiratory failure rate, mechanical ventilation utilization rate, and lower CAT and mMRC scores ( P < 0.05). The levels of interleukin-13 and eosinophil cationic protein in sputum in the eosinophilic group were higher than those in the noneosinophilic group ( P < 0.05), and there was no significant difference in the serum between the two groups ( P > 0.05). The receiver operating characteristic (ROC) curves of sputum interleukin-13 and eosinophil cationic protein predicting peripheral blood EOS% ≥2% of AECOPD patients were statistically significant ( P < 0.05). The noneosinophilic group had a higher rate of rehospitalization due to acute exacerbation during the one-year follow-up, and there was no significant difference in mortality between the two groups. The results show that eosinophils in peripheral blood are a simple, convenient, and inexpensive index for assessing the condition and prognosis of AECOPD patients. Interleukin-13 and eosinophil cationic protein are involved in the pathogenesis of eosinophilic AECOPD and may be the new targeted anti-inflammatory therapies in the future. Impact statement Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an inevitable trend in the development of the disease and eosinophils (EOS) participate in inflammation process. It is important to explore some relatively simple biomarkers in AECOPD which are useful to recognize the disease. In the present study, 108 hospitalized patients with AECOPD were collected and the levels of IL-13 and ECP in the serum and sputum were measured. The levels of IL-13 and ECP in sputum in the eosinophilic group were higher than those in the noneosinophilic group. Moreover, the noneosinophilic group had a higher rate of rehospitalization due to acute exacerbation during the one-year follow-up. The results show that eosinophils in peripheral blood are a simple, convenient, and inexpensive index for assessing the condition and prognosis of AECOPD patients. IL-13 and ECP are involved in the pathogenesis of eosinophilic AECOPD and may be the new targeted anti-inflammatory therapies.