Background Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease. Angiopoietin is an intrinsic mediator induced by T helper 2 cytokines and has been reported it to play a critical role in the pathogenesis of AD. Objectives To determine the relationship between circulating angiopoietin-2 (Ang-2) in AD patients and to determine its correlation with the severity and chronicity of the disease. Methods The present study included 38 AD patients and 38 healthy controls, age- and sex-matched. We collected 3 mm of venous blood from each subject. Enzyme-linked immunosorbent assay (ELISA) determined serum angiopoietin. We determined the correlation between serum Ang-2 level, duration of disease, severity, type of atopy, and scoring atopic dermatitis (SCORAD) score. Results There were highly significant differences between patients and controls with regard to serum Ang-2 levels (P < 0.001). There were significant differences between severe AD patients with serum Ang-2 levels with an increasing level of degree severity (P < 0.001). There were significant differences in serum Ang-2 levels among widespread type (P < 0.03). There was a positive significant correlation between Ang-2 levels and both duration and SCORAD score of the patient group. Conclusion Serum Ang-2 levels may correlate with disease severity, chronicity in patients with AD, and serve as a potential biomarker of the disease severity.