Although(,) vascular remodeling is a hallmark of many chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, anti-vascular strategies to treat these conditions have received little attention to date. We investigated the anti-inflammatory activity of systemic blockade of VEGF-A by the inhibitory monoclonal antibody G6-31, employing a therapeutic trial in a mouse model of psoriasis. Simultaneous deletion of JunB and c-Jun (DKO*) in the epidermis of adult mice leads to a psoriasis-like phenotype with hyper- and parakeratosis and increased subepidermal vascularization. Moreover, an inflammatory infiltrate and elevated levels of cytokines/chemokines including TNFalpha, IL-1alpha/beta, IL-6, and the innate immune mediators IL-22, IL-23, IL-23R, and IL-12p40 are detected. Here we show that anti-VEGF antibody treatment of mice already displaying disease symptoms resulted in an overall improvement of the psoriatic lesions leading to a reduction in the number of blood vessels and a significant decrease in the size of dermal blood and lymphatic vessels. Importantly, anti-VEGF-treated mice showed a pronounced reduction of inflammatory cells within the dermis and a normalization of epidermal differentiation. These results demonstrate that systemic blockade of VEGF by an inhibitory antibody might be used to treat patients who have inflammatory skin disorders such as psoriasis.