Objective To observe the expression and diagnostic significance of periostin in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods In this study 62 patients with AECOPD (AECOPD group) and 35 patients with stable chronic obstructive pulmonary disease (SCOPD group) who were hospitalized in our department from February to November of 2017 were randomly selected. At the same time, 40 healthy patients were selected as a control group. All subjects completed uniform questionnaires and finished blood tests and lung function tests. The measured data were statistically analyzed. Results There were significant differences in smoking, white blood cell count, neutrophil count, periostin, FEV1/FVC, eosinophil count, CAT score and mMRC score among the three groups (P < 0. 05). Periostin was negatively correlated with eosinophil count (P < 0.05), but not correlated with CAT score or mMRC score (P > 0.05). The area under the ROC curve for diagnosis of AECOPD with periostin combined neutrophil count and CAT score was 0.930 (95% CI: 0.875, 0.986), the sensitivity was 0.887 (95% CI: 0.782, 0.947), the specificity was 0.886 (95% CI: 0.735, 0.961). Conclusions Periostin combined with neutrophil and CAT score can be used as an indicator for the diagnosis of AECOPD.