Psoriasis is an immune-mediated inflammatory skin disease associated with comorbidities. Angiogenesis plays a pivotal role in psoriasis pathogenesis which contributes to the initial events that trigger an autoimmune inflammatory response. Angiopoietins 1 and 2 are glycoproteins. Their binding to the tyrosine kinase receptor is essential to angiogenesis. Dysregulation of angiopoietins together with angiopoietin-2 overexpression induce vascular destabilization and regression. This study aimed to explore the relationship between systemic angiopoietin-2 and psoriasis severity. A total of 45 psoriasis vulgaris patients and 45 matched healthy controls were enrolled in the study. The severity of disease was evaluated by Psoriasis Area and Severity Index. Angiopoietin-2 serum level was measured using enzyme linked-immunosorbent assay. The relation between serum level of angiopoietin-2 and psoriasis severity was assessed. Angiopoietin-2 serum level was significantly more elevated in patients than controls (p < 0.001). Angiopoietin-2 serum level was indicatively direct correlated with disease severity (r = 0.7, p < 0.001) with 100% sensitivity and 90.9% specificity in identifying mild and moderate to severe psoriasis patients. Serum angiopoietin-2 directly correlates with psoriasis severity. Angiopoietin-2 is nominated to be a potential sensitive biomarker for the ongoing inflammatory process to monitor the clinical and therapeutic outcomes in psoriasis patients.