The objective of this study was to evaluate the in vitro and ex vivo percutaneous absorption of chlorpheniramine maleate (CPM) from different hydrogel formulations. Various concentrations of polymers, including hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC) and methyl cellulose (MC) were used in the hydrogel formulations. All experiments were conducted using cellulose dialysis membrane. The passive permeation of CPM was affected by the polymer concentrations. The effect of each polymer on the release rate of CPM was found to be statistically different (P<0.05). The formulation which exhibited maximum drug release through cellulose membrane was then used with other membranes namely polyurethane membrane, rat skin and human skin. The release rate of CPM from different membranes was found to be statistically different (P<0.05). Within the different diffusional barriers rat skin was found to be best alternative to human skin. It seems suitable the use of cellulose derivatives for topical application of CPM to obtain high therapeutic concentration at the application site. The synthetic membranes can be used to assess product performance in quality assurance but give little indication of its performance ex vivo.