Background: Psoriasis is an inflammatory skin disorder whose cause is unknown. Psoriasis appears to be an immune-mediated disease, according to growing evidence. The immunomodulatory effects of lenalidomide inhibit the production of pro-inflammatory cytokines that have been associated with several hematologic cancers. Lenalidomide enhances the host's immune system by regulating T cell proliferation, which causes alterations in inflammation that are associated with the etiology of psoriasis. The purpose of the study: In this trial, the aim was to study the effectiveness of lenalidomide as an ointment in the treatment of psoriasis-induced in mice and to examine the histological differences between the tested groups. Materials and methods: This study was conducted from November 2021 to June 2022. 70 healthy male albino mice, which were randomly divided into seven groups of 10 mice each. Psoriasis was induced by imiquimod in groups (1, 2, 3, 4, 5 and 6). Group 1 received only 5% imiquimod cream, Group 2 received Clobetasol ointment, Group 3 received only the base containing lenalidomide and Groups (4, 5, and 6) received lenalidomide ointment (1%, 2% and 3%, respectively).