The aim of this study was to develop and characterize montelukast sodium loaded niosomal drug carrier systems. The vesicles were prepared by film hydration technique using different surfactants. The optimized formulation was selected on the basis of results obtained from drug entrapment, morphology and in vitro drug release studies, and further evaluated for possible drug-excipient interaction, thermal behavior and drug physical state, before and after formulation using Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction analysis methods, respectively. The morphological characterization of vesicles was done using Transmission electron microscopy. Energy-dispersive X-ray spectroscopy system was used for elemental and dimensional analysis of developed vesicles. The vesicle surface charge was determined using zeta potential measurements. The results suggested that the optimized formulation had small size (103±6.01 nm) and high drug entrapment (72.20±2.10%). No chemical interaction was observed between the drug and excipients. The study revealed that Span 60 is a good nonionic surfactant for vesicle formulation. After 3 months storage at 2-8°C, the optimized formulation preserved stability in terms of formulation colour, drug amount and percent drug release. After 3 months, flocculation occurs and hard cake was not formed on the settlement of vesicles. The preliminary results of this study suggest that the designed vesicles could enhance drug entrapment, reduce the initial burst release of drug and modulate the drug release.