This study assessed the feasibility of the transdermal administration of a formulated loratadine-EVA matrix containing an enhancer in rats by comparing the pharmacokinetic parameters of loratadine. A loratadine-EVA matrix (12mg/kg) was applied to the abdominal skin of rats. After transdermal administration of a single 12mg/kg dose of loratadine to rats, the AUC of transdermal administration with and without the enhancer was 2,175±34.0h·ng/mL and 1,153±184.5ng/mL, respectively. The relative bioavailability of the loratadine-EVA matrix containing N-methyl 2-pyrrolidone administered by transdermal route was approximately 1.86-times higher than that of the control group (p <0.01). The antihistamine effect loratadine from the EVA matrix containing the enhancer and plasticizer was determined using the Evans blue dye procedure by comparing the changes in the increase in vascular permeability after transdermal application. Transdermal application of the loratadine-EVA matrix containing diethyl phthalate and N-methyl 2-pyrrolidone inhibited the increase in vascular permeability induced by histamine by 33.96%, whereas the loratadine-EVA matrix without the plasticizer and enhancer produced only 20.33% inhibition. This suggests that the transdermal application of a loratadine-EVA matrix containing a plasticizer and enhancer decreases the histamine-induced vascular permeability in the conjunctiva. In conclusion, the loratadine-EVA matrix system containing a plasticizer and enhancer may find applications as a transdermal delivery system providing an increased constant plasma concentration and superior antihistamine effects.