In this book stable nanoparticles of pioglitazone HCL were prepared using biodegradable polymer, to increases bioavailability and to control release of drug. PGZ is used for the treatment of diabetes mellitus type 2. The drug modulates the transcription of the insulin-sensitive genes involved in the control of glucose and lipid metabolism in the muscular tissues and in the liver. It is an activator of the intracellular peroxisome proliferator-activated receptor-γ, and decreases metabolic and vascular insulin resistance causing rise in HDL-cholesterol plasma in humans. However, the poor aqueous solubility of PGZ may cause low bio absorption and limited therapeutic efficacy. So, the aim of the present study was to prepare stable PGZ loaded polymeric nanoparticles, to enhance the solubility and improve the bioavailability of the drug.