Objective To study the therapeutic effect of sea buckthorn oil on allergic contact dermatitis (ACD) in mice. Methods A total of 60 ICR mice were randomly divided into 6 groups:blank control group, model control group, three groups of high-dose, medium-dose and low-dose sea buckthorn oil (100%, 50%, 25%, ad us. ext.), respectively, and positive control group (compound dexamethasone acetate cream), with 10 mice in each group. The mouse model of ACD was established by sensitization and stimulation with 2,4-dinitrochlorobenzene (DNCB), and injuries in the ear skin of the mice were scored and used as the indicator of successful establishment of the model. The degree of ear swelling and the spleen index of the mice in each group were measured at 48 h after stimulation. Hematoxylin and eosin staining was used to observe the pathological changes in the mouse ear skin. Results Measurement of the degrees of ear swelling showed that the high-dose sea buckthorn oil group (9 mL/kg, ad us. ext.) obviously inhibited the DNCB-induced ear swelling in the mice, with a significant difference compared with the model group (P< 0.01) and non-significant difference compared with the positive control group (P> 0.05). The result of the spleen index assessment showed that sea buckthorn oil at each dose may play an immune-regulatory role by promoting the development of immune organs. The pathological examination showed that epidermis thickening of the ear tissue, epidermal and dermal edema and infiltration of lymphocytes were reduced, dermal vasodilatation and congestion were alleviated, and inflammatory cell infiltration was inhibited in the three groups of different doses of sea buckthorn oil compared with the model control group. Conclusions Sea buckthorn oil has an obvious inhibitory effect on the DNCB-induced allergic contact dermatitis in mice. However, its related mechanisms remain to be further investigated.