Objective:To explore the effect of bacilli Galmette-Gurin (BCG)-polysaccharide nuceic acid on atopic dermatitis in mice and its mechanism. Methods: Forty NC/Nga mice were selected and randomly divided into Group A (model group), Group B (dexamethasone treatment group), Group C (BCG polysaccharide nucleic acid treatment group) and Group D (control group) with 10 mice in each group. Atopic dermatitis model were constructed by applying 2, 4-dinitrochlorobenzene on the skin of the mice. Mice in Group D were treated with acetone solution (100μL) on the foot pad and abdomen after hair removal at the age of 7 weeks, then on ear skin at the age of 8-13 weeks. For mice in A, B and C groups, 100μL of acetone solution containing 2, 4-dinitrochlorobenzene was applied to the foot pad and the abdomen at the age of 7 weeks, then on ear skins at the age of 8 to 13 weeks. At the age of 7-13 weeks, mice in Group A and Group D were treated with 100μL saline (i.p.);mice were given dexamethasone (0.1 mL/kg, i.p.) every other day for 7 weeks in Group B;mice were treated with BCG polysaccharide nucleic acid (0.5 mg/kg, i.p.) every other day for 7 weeks in Group C. The ear thickness was measured every week and the scratching frequency was recorded 1 times for 10 min a week. The mice were sacrificed after the last administration of drugs. IgE, IL-4, IL-10, IL-12 and IFN-γin the plasma were detected using ELISA, and RT-PCR method was employed to detect the concentrations of IL-4, IL-10, IL-12 and IFN-γproteins. After HE staining, the lesion degree of inflammation in ear tissue was observed microscopically. Results:The ear thickness and scratching frequency of Group A were significantly higher than those in group B, C and D (P<0.05), and there was no significant difference between Group B and C (P>0.05);the concentrations of IgE, IL-4 and IL-10 in the plasma and the expression of IL-4, IL-10 mRNA in the spleen tissues of Group A, B and C were all significantly higher than those of Group D (P<0.05);the concentrations of plasma IL-12 and IFN-γ, and spleen protein expression of IL-12 and IFN-γin Group C mice were significantly higher than those of Group A (P<0.05). Histological observation showed obvious ear tissue exudation, erythema, swelling, desquamation of skin, and scabbing in Group A. Histopathology of the skin lesion also showed hyperkeratosis, focal-parakeratosis, stratum spinosum hypertrophy, mild sponge-like edema, a large number of lymphocytes along with plasma cell infiltration in dermis, angiectasis and hyperemia in Group A, while degree of ear skin lesion in Group B and D mice was significantly lighter than that of Group A. Conclusions:BCG polysaccharide nucleic acid can significantly reduce the serum IgE concentrations, increase the expression of IL-12, IFN-γprotein, correct the imbalance of Thl/Th2 in atopic dermatitis mice, and has obvious inhibitory effect on atopic dermatitis in NC/Nga mice.