Objective: To investigate the clinical value of combined detection of serum angiopoietin 2 (Ang-2) and Clara cell protein 16 (CC16) in the early diagnosis of acute respiratory distress syndrome (ARDS). Methods: Two hundred critical patients, treated at the Department of Critical Care Medicine, Bao'an District People's Hospital, Shenzhen during March 2015 and September 2016,were included in the study. According to the Berlin standard, patients were divided into two groups (n=100 each group): the ARDS group and non-ARDS group.The serum levels of Ang-2 and CC16 were measured by enzyme-linked immunosorbent assay (ELISA) on the first and second day of admission for each patient, in addition to completing APACHEⅡ score, medical history, vital signs collection and other biochemical indicators detection. Finally, paired-samples t test was used to analyze the data. The multiple ROC curve was used to calculate the area under the curve of the reference index of the serum levels of Ang-2 and CC16 on the first and second day. Results: On the first and second day, the serum levels of Ang-2 and CC16 were significantly higher in ARDS patients than those in non-ARDS patients, and there was a correlation between the serum levels of Ang-2 and CC16 in ARDS patients. The ROC curve showed that the combined detection of Ang-2 and CC16 on the first day achieved a highest sensitivity of 75.9% and detection of CC16 on the first day achieved a highest specificity of 70.2%. Conclusion Single-detection of serum levels of Ang-2 and CC16 could be used for early diagnosis of ARDS, and the combined detection of both has a higher sensitivity than single detection.