The objective of the present investigation was to enhance the solubility of practically insoluble glipizide by preparing its nanoparticles. The glipizide nanoparticles were prepared by anti-solvent precipitation method using various drug-to-stabilizers ratio. The nanoparticles of glipizide were evaluated for particle size, zeta potential, saturation solubility, and dissolution behavior. Glipizide nanoparticles showed particle size of 425.6 nm and zeta potential of −16.2 mV. Saturation solubility of pure glipizide and nanosuspension were 0.19±0.006mg/20ml and 4.3±0.18 mg/20ml respectively, showing more than 22.63 times increase in solubility. Differential scanning calorimetry (DSC) showed that crystalline state of glipizide remained unchanged in glipizide nanosuspension. In glipizide nanosuspension, 59.57±0.63% of the drug released within 10min and almost 100±0.2% within 60min, while micronized suspension of glipizide showed only 8.91±0.58% release at the end of 5min and 18.21±0.25% release in 60 min. From the results, it was concluded that significant enhancement in solubility of glipizide in phosphate buffer (pH 6.8) thus enhancement in dissolution of it when formulated as drug nanoparticles.