Cutaneous Tuberculosis is also known as dermal tuberculosis or tuberculosis cutis (extrapulmonary tuberculosis) which can occur in any age group and patients who may or may not be suffering from pulmonary tuberculosis. The current treatment given for the disease is oral therapy of anti-tubercular drugs which has many side effects such as hepatotoxicity, headache, anxiety, euphoria, insomnia, eosinophilia, hepatitis. Hence to avoid these side effects and to increase efficiency of current therapy a topical proniosomal gel of isoniazid was formulated. Coacervation phase separation method was used and proniosomal gel was formulated by using Span 20, soya lecithin, and cholesterol. Optimum concentration of 3 factors Span 20, soya lecithin, and cholesterol were determined using Box Behnken design with at 2 levels and vesicle size and entrapment efficiency as responses. The optimized proniosomal gel was characterized by vesicle size, entrapment efficiency, transmission electron microscopy (TEM), in vitro drug release, skin retention studies, skin irritation studies and stability studies. The optimised batch showed vesicle size of 2.27±1.82 µ, and entrapment efficiency of 98.15±0.25 %. The optimised formulation was stable under refrigeration condition (5°C) in amber coloured bottle, was non-irritating and showed 98.10±1.28 % release and 85±1.53 % permeation after 6 h and 436±12 µg drug was retained in the skin after 3 hrs.