Neopterin is an immunological marker of cellular immune activation. Etanercept is a tumor necrosis factor-α (TNF-α) antagonist that decreases excessive levels of TNF-α associated with inflammatory disease down to physiological levels. The objective of this study was to investigate urine neopterin levels in psoriatic patients treated with etanercept, to study the effect of etanercept as a TNF-α blocker on urine neopterin levels. Urine neopterin levels and urine neopterin/creatinine ratios were measured by high-performance liquid chromatography in 22 patients with psoriasis before and after treatment with etanercept. Results were compared with a group of 20 healthy volunteers, and 20 patients with inflammatory skin diseases as control groups. Urine neopterin levels, neopterin/creatinine ratios and Psoriasis Area and Severity Index (PASI) scores were evaluated at baseline, and the 12th and 24th week after treatment. Urine neopterin levels were significantly elevated in the psoriatic group compared with control and inflammatory skin diseases groups (P < 0.05). Urine neopterin levels were significantly reduced after etanercept treatment. Statistically we did not find any correlation between neopterin levels and PASI scores. Our findings indicate that urine neopterin concentrations may reflect the disease activity in psoriasis, and may be used as a marker for monitoring disease activity and response to treatment with etanercept in psoriatic patients.