Background: Diabetes is a common comorbidity among patients with exacerbation of chronic obstructive pulmonary disease (AECOPD). Diabetes has been reported to be associated with length of stay (LOS), death, and cost among AECOPD patients. However, most studies are retrospective or have small sample sizes. The association for cost has not been researched using diabetes as a main analytic factor. This study aimed to fill gaps mentioned above, to compare basic characteristics between the diabetic and non-diabetic group, and to detect associations between diabetes and clinical outcomes among patients hospitalized with AECOPD. Methods: A total of 5334 AECOPD patients, classified into diabetic and non-diabetic group, were included from a prospective multicenter patient registry study. Generalized linear regression and logistic regression were separately used for the association between diabetes and direct hospitalization cost and the association between diabetes and LOS. Results: Generally, diabetic patients had a more severe profile, including being older, more overweight or obese, having more former smokers, more emergency room visits in the past 12 months, and more comorbidities occurrence. Diabetic patients also had worse clinical outcomes, including higher cost and longer LOS. Additionally, the generalized linear regression indicated that the marginal mean cost difference between diabetic and non-diabetic patients was RMB 775.7. Conclusions: AECOPD patients with comorbid diabetes had a more severe profile and higher direct hospitalization cost. Diabetes screening and integrated care programs might help reduce the heavy comorbidity and economic burden. Moreover, corticosteroids and metformin could be considered in the treatment of these patients. Trial registration Clinicaltrials.gov with the identifier NCT0265752.