Psoriasis, one of the most prevalent inflammatory diseases in dermatologic pathology, remains a challenge in regards to the therapeutic approach. Topical therapy for psoriasis is a current trending subject as it implies good compliance for the patient, few adverse systemic reactions and a targeted effect. Numerous substances are now being tested, from natural to synthetic compounds and already known substances in improved formulas such as vesicular systems. The aim of this article was to conduct a literature review regarding the topical therapy of psoriasis in animal models, between June, 27, 2019 and July 9, 2020. For this article, the authors conducted extensive research in PubMed with the following keywords: Psoriasis AND (topical OR local) and (therapy OR treatment) AND (mice OR rats). The main new studied substances included lycopene, sodium butyrate, salvianolic acid B, small interfering RNAs (siRNAs) in ionic liquids, albendazole, phosphodiesterase inhibitors, biomimetic reconstituted high-density lipoprotein nanocarrier gel containing microRNA (miRNA)-210 antisense, thymoquinone in ethosomal vesicle, Sea buckthorn oil (), nitidine chloride, extract and [1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol (CIM). New formulas of already known anti-psoriasis substances such as: Cyclosporine, methotrexate, calcipotriol, tazarotene, protein kinase p38 and integrin α5β1 as a target, are also reviewed. Recent research in topical psoriasis underlines the importance of animal experimental research in dermatology, providing a starting point for developing new therapeutic approaches in one of the most frequently diagnosed chronic dermatologic diseases. Vesicular systems are now providing the best vehicle for topical therapy, thus easing the action of the active substances at their target sites.