Several studies suggest that microangiopathy plays a crucial role in the pathogenesis of psoriasis. TNF-alpha up-regulates the genetic transcription of VEGF, a pro-angiogenetic cytokine over-expressed in psoriatic skin, which promotes micrangiopathic modifications in psoriatic plaque. Etanercept is a chimeric protein used in the treatment of psoriasis and other immunomediated disorders, which blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. Starting from this data, we retain that Etanercept can improve microangiopathy in psoriatic skin by reducing the synthesis of pro-angiogenetic chemokine VEGF. The aims of the study are: to verify the effect of Etanercept on cutaneous en plaque capillaries in vivo using intra-vital videocapillaroscopy analysis, to evaluate the relation between the en plaque videocapillaroscopic pattern and the immunohistochemical cutaneous expression of VEGF in psoriasis, and finally to correlate all these in data with clinical disease activity. Eighteen patients (10 male and 8 female, mean age 51, range 21–60) suffering from stable, en plaque type psoriasis, involving at least 10% of body surface area (BSA), and not responsive to conventional therapy were included in the study. All the enrolled patients received Etanercept 50mg/twice/week, subcutaneously, for 12 weeks, and were carefully followed up for clinical response with PASI score and DLQI index both before (T₀) and after 12 weeks (T₁₂) of treatment with Etanercept. A well-demarcated psoriatic plaque of the extensor surface of upper extremities was chosen to perform an intra-vital videocapillaroscopy analysis (IVCP), and a skin biopsy for immunohistochemical study both at T₀ and T₁₂in all the included patients, in order to evaluate the presence of microangiopathy and its modification after therapy. All the patients experienced a clinical improvement of cutaneous disease with a significant decrease of PASI score (p0.0001) and DLQI level (p0.0001), throughout the twelve weeks of treatment. On IVCP analysis, microangiopathy dramatically decreased (p0.0001), this modification being significantly related with PASI and DLQI decrease at T₁₂. Immunohistochemical expression of VEGF decreased significantly from T₀ to T₁₂ (p0.0001), and was related with a reduction of psoriatic microangiopathy at T₁₂. The results of our videocapillaroscopic and immunohistochemical investigation confirm that the therapeutic potentiality of Etanercept is based also on its capability to promote the regression of psoriatic microangiopathy. Moreover, according to these considerations, videocapillaroscopic evaluation of psoriatic plaque, both before and after treatment with Etancercept, may be a useful tool to objectively demonstrate its effect on microcirculation.