Excess stripping of stratum corneum (SC) layers by patch-peeling from the skin surface is one cause of skin irritation. High SC hydration by patch occlusion may also cause skin irritation, although the occlusive technique is preferable to increase the skin permeation of topically applied drugs. In the present study, film having a honeycomb structure was selected as the backing layer of a drug-in-adhesive (DIA) patch to reduce peeling of the SC without losing adhesion force to the skin surface, as well as decreasing the skin permeation of a model drug, tulobuterol. The usefulness of the DIA patch with honeycomb film was evaluated by transepidermal water loss (TEWL) changes, amount of SC removed by patch-peeling, distribution pattern of removed SC on the adhesive layer, and water permeation through the patch. Furthermore, skin permeation and release profiles of tulobuterol from the DIA patch were investigated. Significantly (p<0.05) less TEWL change was observed after removal of the patch with a honeycomb film compared with the conventional pressure-sensitive adhesive patch, and no difference in tulobuterol permeation through skin from the patches was confirmed regardless of the type of backing layer. In addition, a lower amount of SC was removed by the peeling of the patch with a honeycomb film. The results suggest that DIA patches with a honeycomb film as a backing layer may be used to achieve less SC removal without reducing the skin permeation of drugs.