The topical efficacy of baicalin, a natural flavonoid isolated from Scutellaria baicalensis Georgi, which has several beneficial properties, such as antioxidative, antiviral, anti- inflammatory and antiproliferative, is hindered by its poor aqueous solubility and low skin permeability. Therefore, its incorporation into appropriate phospholipid vesicles could be a useful tool to improve its local activity. To this purpose, baicalin at increasing concentrations up to saturation, was incorporated in ultradeformable vesicles, which were small in size (similar to 67 nm), monodispersed (PI < 0.19) and biocompatible, regardless of the concentration of baicalin, as confirmed by in vitro studies using fibroblasts. On the other hand, transdermal flux through human epidermis was concentration dependent. The in vivo results showed the significant anti- inflammatory activity of baicalin loaded nanovesicles irrespective of the concentration used, as they were able to reduce the skin damage induced by the phorbol ester (TPA) application, even in comparison with dexamethasone, a synthetic drug with anti- inflammatory properties. Overall results indicate that ultradeformable vesicles are promising nanosystems for the improvement of cutaneous delivery of baicalin in the treatment of skin inflammation