Background: Atopic dermatitis is a chronic inflammatory skin disease that is characterized by recurrent pruritus, dry skin, and eczematous rash, and is extremely difficult to treat. The main therapy for the management of atopic dermatitis includes treatment with glucocorticoids and calcineurin inhibitors, problems with corticosteroid and calcineurin inhibitors in long-term use can cause side effects; therefore, a safe and effective atopic dermatitis treatment therapy is needed to establish better outcome with the least side effect.Aim of the study: To evaluate the possible therapeutic effect of topical vardenafil in induced atopic dermatitis in mice.Methods: The study included fifty Albino male mice of six weeks' age. The mice were randomly divided into five groups (Each group contained 10 mice). A control group without treatment (apparently healthy), and five groups (non-treated induced, vehicle, tacrolimus, and vardenafil treated group) were topically treated once daily with 1-Chloro-2,4-dinitrobenzene solution 1% and 0.2% on the dorsum of the back skin to induce atopic dermatitis. The animals were housed in a private and good ventilated isolated place; with a room temperature of 20-24 degrees C and kept light for 12 hours. Before starting the study, the animals were left for seven days to acclimatize to the animal room conditions and allowed free access to water and Ad libitum feeding. three groups of 10 induced atopic dermatitis mice that treated with (vehicle, 1% tacrolimus, and 1% Vardenafil ointment) topically once daily at 10 AM for 3 weeks, for assessing the effect of different treatments, the flowing parameter will be evaluated, Blood picture (WBC, Eosinophil, neutrophil), histopathological score (hyperkeratosis, parakeratosis, erosion, edema, epidermal thickness, and inflammation), immunohistochemistry (IL4, IL13) and Observational severity score.Results: Levels of WBC, Eosinophil, neutrophil, immunohistochemistry of IL-13 and IL-4, and histopathological scores (hyperkeratosis, parakeratosis, erosion, epidermal thickness, edema, and inflammation) were significantly increased among induced non treated AD group in comparison with the apparently healthy group. In comparison between the effect of the vehicle-treated group with induced non-treated group show no effect on all parameters except (mild erosion and extracellular edema) while In comparison between the effect of Tacrolimus1% ointment treated group with an induced non-treated group in relation to different these parameters show a reduction in this parameter and the most obvious decrease in the level of WBC in comparison with another treated group, the Vardenafil 1% ointment treated group in comparison with the induced non-treated group in relation to different these parameter show significant reduction in WBC, neutrophil, eosinophile, IHC ( IL13, IL4), histopathological score and observational severity score. But the vardenafil treated group has an obvious ability to decrease the level of epidermal thickness, erosion, and parakeratosis Furthermore, in comparison between the effect of Tacrolimus, and Vardenafil treatment on the studied variables regarding histopathological scores; Hyperkeratosis and inflammation were significantly lower after Felodipine and Vardenafil treatment among studied groups.Conclusion: According to the results obtained from this study, all studied groups (Tacrolimus and Vardenafil treated group) shows Obvious therapeutic effect in a model of atopic dermatitis in mice. They show significant improvement in the histopathological picture in comparison with the induced non-treated group. Both felodipine and vardenafil show anti-inflammatory effects (decrease IL4, IL13), they also decrease WBC and