The present study involves the preparation of lecithin/chitosan nanoparticles loaded with hydrochlorothiazide (HCT) (a poorly water soluble antihypertensive) and hydrochlorothiazide complexed with beta-cyclodextrin (HCT-beta-CD) with a view to improve its biopharmaceutical properties. Nanoparticles prepared using modified solvent evaporation method showed a particle size in the range of 126-139 and 152-181 nm (polydispersity index, PDI = 0.2) for HCT and HCT-beta-CD loaded nanoparticles respectively. TEM images revealed their spherical nature. The stable nature of the prepared formulations was evident from the high positive value of zeta potential (>20 mV). HCT and HCT-beta-CD loaded nanoparticles with 150 mg of drug have shown a maximum entrapment efficiency of 81.8 +/- 1.7% and 91.1 +/- 1.5% respectively. In vitro studies have shown an improved and a sustained release pattern. In vivo activity in DOCA induced hypertensive rats demonstrates 1.5-fold percentage decrease in systolic blood pressure and a prolonged duration of action.