Background Vitiligo is a common pigmentary disease that affects 0.5% to 1% of the global population. The main manifestation of vitiligo is skin depigmentation, which significantly influences appearance and brings enormous psychological stress for patients. C-X-C motif chemokine ligand 9 (CXCL9), CXCL10 , CXCL11 and CXCL12 are linked to the Th1 pattern and have been suggested as one of the most relevant chemokine axes that promote T cell migration in different autoimmune and inflammatory process . These were suggested to promote melanocyte-specific cytotoxic T lymphocyte (CTLs) to infiltrate into the basal layer of the epidermis to attack melanocytes, resulting in the deficiency of melanin. Objective The aim of this study was to evaluate the role of CXCL10 and CXCL12 in the pathogenesis of vitiligo and to detect its relationship to disease activity. Methods Forty patients with non-segmental vitiligo (NSV; 20 patients with active disease and 20 stable patients). This group included 20 male patients and 20 female patients, with ages ranging from 10 to 65 years. Twenty healthy age- and sex-matched controls were included. The control group included 10 males and 10 females with ages ranging from 10 to 65 years. We measured the serum level of CXCL10 and CXCL12 in the patients and controls using the enzyme-linked immunosorbent assay (ELISA) method. Results Serum CXCL10 level was highly significantly increased in patients with vitiligo compared to controls. There was a high statistically significant difference between patients with active disease and those with stable disease regarding serum level of CXCL10 with higher level of CXCL10 in active type. Conclusion Our results suggest that vitiligo might be associated with increased serum levels of CXCL10 and CXCL12. There is a positive relationship to disease activity, indicating that CXCL10 and CXCL12 may play a significant role in the pathogenesis of vitiligo.