Abstract: OBJECTIVE To develop a simple and effective method to efficiently assess the effect arising from transdermal absorption of the penetration enhancer, and to compare the effect of the penetration enhancer assessed using the comprehensive principal component analysis method and the skin resistance method. METHODS In this study, aminophylline was adopted as a model drug, and azone, menthol, borneol, oleic acid and their combination were employed as the permeation enhancers. The isolated back skin of SD rats was applied as a permeation barrier. The drug concentration in the receiving solution was measured using HPLC. Moreover, cumulative permeability, permeability coefficient, steady flow rate, lag time and infiltration multiple were calculated, and the effect of permeability promotion was comprehensively assessed through a principal component analysis. The changes of skin resistance over time were measured to assess the effect arising from penetration enhancers on skin. RESULTS The results were achieved using the Franz diffusion cell method combined with the comprehensive principal component analysis method, indicating that oleic acid plus borneol and menthol had a penetration promoting effect on aminophylline, and the penetration promoting effect of oleic acid and borneol was higher than that of menthol. The penetration promoting substances measured by skin resistance included oleic acid plus borneol, menthol plus azone, menthol, azone, oleic acid, borneol plus azone and menthol plus borneol, and the effect degree decreased in descending order. The penetration promotion effect assessed by the skin resistance method was basically parallel to that assessed through the in vitro transdermal absorption experiment(r=0.886 9). CONCLUSION Both the integrated principal component analysis method and the skin resistance kinetics method are found to be capable of objectively assessing the effect of the penetration enhancer, and the two methods are obviously correlated with each other.