The aim of this work was to investigate the percutaneous absorption of flurbiprofen (FP) using counter-ions as enhancers as well as to compare their enhancing activity with penetration enhancers in vitro. The in vitro permeation studies of FP were performed in isopropyl myristate (IPM) solution by two-chamber diffusion cells, using rat abdominal skin as a model. Among the penetration enhancers examined, including the cosolvents of propylene glycol and ethanol (EtOH), oleic acid, menthol, laurocapram, sorbitan monooleate, and N-methyl-2-pyrrolidone (NMP), 10% (w/w) EtOH and NMP exhibited the most potent solubilization and enhancing effects of FP from IPM, with a flux of (372.60 AE 45.12) mg/cm 2 /h and (474.21 AE 46.64) mg/cm 2 /h, respectively. Ten percent (w/w) EtOH/IPM binary system was used to investigate the effect of the counter-ions, namely diethylamine (DEA), triethylamine (TEA), ethanolamine (EtA), diethanolamine (DEtA), triethanolamine (TEtA), and N-(2 0 -hydroxyethanol)-piperdine (HEPP). The cumulative amounts were markedly increased in the presence of the counter-ions, and the highest flux of (1297.53 AE 121.81) mg/cm 2 /h was obtained by DEA. This was related to the decreased lipophilicity and different physicochemical properties of the ion-pairs. In particular, we proved the formation of an FP/amine ion-pair in solution by 1 H-NMR. The results suggest that the counter-ions are more efficient than penetration enhancers.