ObjectiveTo assess the efficiency of a Sophora flavescens Ait (S. flavescens, Ku Shen)-soluble microneedle (SFA-MN) for improving skin lesion symptoms in mice with psoriasis.MethodsSFA-MNs were prepared using a two-mold molding process with 20% w/v polyvinylpyrrolidone and 15% w/v polyvinyl alcohol. The SFA-MNs were assessed for morphology, mechanical properties, in vitro dissolution, identification of components, and skin lesion improvement in imiquimod-induced psoriasis mice.ResultsThe SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis, facilitating efficient drug delivery. Furthermore, they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differentiation 3 and tumor necrosis factor-α. In addition, this system alleviated skin inflammation, splenic swelling, and thymic atrophy in the psoriasis-like mouse model. Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios (m/z) of the secondary fragments N-methylcytisine, 5α, 9α-dihydroxymatrine, sophoramine, matrine, oxysophocarpine, oxymatrine, and kushenol O.ConclusionThe drug delivery strategy combining traditional herbal S. flavescens with soluble microneedle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models, enabling enhanced therapeutic effects compared with the control group.