Most of the drug fraction penetrating the skin after topical application is taken up by the cutaneous blood flow, although the rest directly migrates into deeper tissues such as the subcutis and muscle. A new in situ experimental hairless rat model was designed to distinguish these fractions of topically applied drugs. Flurbiprofen, a non-steroidal anti-inflammatory drug, was selected as the model drug. In this model, two agar gel discs were subcutaneously inserted into the abdominal region of hairless rats as a drug receptor, and a topical formulation containing the drug was placed above either side of the gel disc. Plasma and agar levels of flurbiprofen were followed every 2 h over 10 h. The migration fraction of the drug into the systemic circulation and that directly to subcutaneous tissues were calculated to be 99.8% and 0.2% against the total amount which penetrated the skin, and the drug ratios into agar gel from the systemic circulation and not from the systemic circulation (i.e. directly migrated from the formulation) were 16.0% and 84.0%, respectively, at 10 h. This in situ drug disposition profile in skin was similar to the in vivo profile calculated from the in vivo muscle amount of flurbiprofen using muscle clearance. These results clearly suggest that the present in situ experimental model is a valuable tool for easy analysis of the skin disposition of topically applied drugs.