ABSTRACT Background: Alopecia areata (AA) is a non-cicatricial alopecia that is postulated to be a hair-specific autoimmune disease, with genetic factors playing a role in disease susceptibility and severity. The disease presentation ranges from circular patches on the scalp to complete hair loss with devastating psychosocial consequences. Patients and methods: This was a case control study carried out on 40 patients diagnosed as alopecia areata. They were recruited from the outpatient clinic of Dermatology, Andrology and STDs Department, Mansoura University Hospitals. In addition 40 normal healthy subjects with matched age and sex were selected to act as a control group. Results: Serum levels of IL-21 were significantly increased in AA patients, and showed significant positive correlation with activity of the disease. Higher serum levels of IL-21 in active cases support its role as predictor of disease activity. There were no significant differences in IL-21 level with different SALT scores. Receiver Operating Characteristic (ROC) curve analysis of IL-21 was conducted to evaluate the sensitivity and specificity of serum IL-21 as a diagnostic index for AA. The AUC-ROC of IL-21 was excellent (0.962); and the best cut off point for IL-21 was determined to be 22.22 pg/ml. It was good predictive value. Its accuracy was 86.3%. Conclusions: The results of this study indicate that the serum IL-21 could be promising marker in the diagnosis of alopecia areata, and also can be used as prognostic marker of its activity.