Abstract: Objective To optimize the formulation of an emollient for treatment of atopic dermatitis prepared using ceramide, sodium hyaluronate, paeonol, and camellia-seed oil. Methods The emollients with different ratios of the 4 components were designed according to the L9 （34）orthogonal table with 4 factors and 3 levels. The efficacy of the prepared emollients was tested in 4-6 week-old BALB/c mouse models of atopic dermatitis to determine the optimal formulation of the emollient by evaluating skin water content, transepidermal water loss (TEWL), pharmacodynamics and skin irritation. Results Range analysis of the orthogonal table and analysis of variance showed that ceramide and camellia seed oil contents had the greatest impact on the skin water content and TEWL, respectively, and the optimal composition of the emollient contained the 4 components at the ratios of D1E1F1G1. Pharmacodynamic experiments showed that at high, medium and low doses, the emollient with the optimal formulation significantly improved the skin water content, pH and TEWL in the mice (P<0.05) with similar effects in the positive control group (P>0.05) and a skin irritation test score of 0. Conclusion The emollient we prepared can significantly improve skin water content, pH and TEWL in the mouse model of atopic dermatitis without skin irritations.