Aim:This work aimed to develop topical nanoemulsion gels of cetirizine, a second-generation antihistamine, to avoid its oral intake drawbacks and enhance skin permeation. Methods:Cetirizine nanoemulsions were formulated and characterised for their particle size, polydispersity index, zeta potential, drug release and drug permeation through rat skin. The optimised formulation, obtained using 2(3)full factorial design, was incorporated in carbopol and chitosan gels and evaluated clinically for urticaria treatment. Results:The optimised formulation had particle size of 32.015 +/- 1.87 nm, polydispersity index of 0.29 +/- 0.04, zeta potential of -19.31 +/- 0.43 mV, cetirizine percent released of 98.50 +/- 1.23% and permeability coefficient of 7.65 cm.h(-1). Cetirizine nanoemulsion gels were more effective than their control gels in urticaria treatment with significant decrease in the degree of wheals and itching and higher recovery percent. Conclusion:Cetirizine nanoemulsion topical gels are expected to be a rational and effective tool for avoiding cetirizine oral side effects and targeting the affected skin.