Mesenchymal stem cells (MSCs) inhibit the proliferation or activation of lymphocytes, and their inhibitory effects do not require human leukocyte antigen (HLA)-matching because MSCs express low levels of HLA molecules. Therefore, MSCs may be able to regulate immune responses. In this study, we determined whether MSCs could inhibit psoriasis-like skin inflammation in mice. After induction of psoriasis-like skin inflammation using intradermal injection of IL-23 or topical application of imiquimod with or without treatment with MSC, mouse skins were collected, and H&E staining and real-time PCR were performed. IL-23-induced skin inflammation was inhibited when MSCs were injected on day -1 and day 7. The expression of proinflammatory cytokines such as IL-6, IL-17, and TNF-α was inhibited by MSC injection, and the expression of chemokines such as CCL17, CCL20, and CCL27 was also decreased in mouse skin. We also determined whether MSCs could not only prevent but also treat psoriasis-like skin inflammation in mice. Furthermore, in vitro experiments also showed anti-inflammatory effects of MSCs. Dendritic cells which are co-cultured with MSCs suppressed CD4+ T cell activation and differentiation, which are important for the pathogenesis of psoriasis. These results suggest that MSCs could be useful for treating psoriasis.