Abstract Background Psoriasis was reported to be a chronic, immune-mediated inflammatory skin disease. Psoriasis can be induced in mice by Imiquimod which is an immune response modifier and it is the most widely used animal model of psoriasis. Nigella sativa oil is frequently used for its antiinflammatory and anti-oxidant activities. The current study is aimed to assess the effect of oral Nigella Sativa oil on imiquimod induced model of psoriasis in thin skin of adult male mice. Materials & methods The current study included twenty male albino mice. After seven days acclimatization period, animals were subjected to shaving of square shaped area 2 x 2 cm2 at the backs of all mice. Then, animals were divided into three groups: Group I: Control, n = 10: subdivided into: Subgroup IA (Negative Control), Subgroup IB: which received a daily dose of 20 mg of Nigella sativa oil orally. Group II, n = 5: Each mouse received a daily topical dose of 62.5 mg IMQ cream on the shaved back skin for fourteen days. Group III, n = 5: Each mouse received a daily topical dose of 62.5 mg IMQ cream on the shaved back skin for fourteen days. On day seven after shaving and 4 hours after application of IMQ cream, each mouse in group III received 20 mg of Nigella sativa oil once daily for seven days. Skin specimens were obtained from the shaved parts of skin of the backs of all animals and were processed for light microscopic examination. Results Imiquimod (IMQ) application led to apparent increased epidermal thickness, apparent thickening of stratum corneum and alterations in the normal appearance of keratinocytes with vacuolation inside their cytoplasm and increased intracellular spaces between cells. Apparently Elongated epidermal rete ridges were observed along with abundant infiltrates of mononuclear inflammatory cells in the dermis. However, oral use of Nigella sativa oil (N.sativa) strongly inhibited IMQ-induced psoriasis-like inflammation and alleviated all epidermal and dermal changes observed after IMQ application. Conclusion N. sativa can be used as an effective treatment for modraete psoriasis.