To assess the effect of topical dapsone in the treatment of atopic dermatitis in comparison with tacrolimus.  A case-control study was done on 80 male Albino mice (20-30g) recruited from local markets, were treated with 1-Chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis and compared with age and the sex-matched control group comprised of 20 healthy male Albino mice. The topical applications of Tacrolimus 0.1% ointment and Dapsone 5% gel were performed on atopic dermatitis area for seven days and fourteen days once daily starting from the fourth day of induction and Complete blood count, IL-4 and IL-13 were measured in skin tissue homogenate in addition to histopathological evaluation of atopic dermatitis skin lesion and assessment of observational severity score and compared with those of controls. The results revealed that the levels of IL-4 and IL-13, total WBC, observational severity score, and the score of all histopathological markers were increased significantly in the group of mice treated with 1-Chloro-2,4-dinitrobenzene (DNCB) for A.D. induction in comparison with controls. These markers were reduced significantly after the topical application of tacrolimus. They showed a comparable reduction but after a longer duration of topical treatment with dapsone after two weeks of treatment. Topical application of dapsone on induced A.D. mice showed a significant reduction in the levels of IL-4 and IL-13, total WBC, observational severity score, and histopathological markers score and these effects were compared to those of topical tacrolimus.