In a novel attempt, nalidixic acid was formulated in different topical 1%(w/w) gel and cream bases. The viscosity, pH and drug content of preparations were investigated. The highest in vitro release was achieved by (Na-CMC) gel base. The presence of isopropanol as a cosolvent and nalidixic acid sodium benzoate solid dispersion (1: 8) in the selected formulae had enhanced both the in vitro release and antibacterial activity of nalidixic acid. Both DSC and FTIR spectroscopy had shown that the drug is compatible with selected excepients. All cream formulations had shown weaker antibacterial activity therefore only gel bases were further investigated for their stability. No significant change in pH or drug content had been observed in stored gel formulations. The best clinical result in impetigo was achieved after 4-7 days with treatment by gel containing isopropanol and nalidixic acid sodium benzoate solid dispersion (1:8).