PLGA nanoparticles loaded with monensin (carboxylic ionophore) were prepared by emulsion solvent evaporation method using PLGA of molecular weight (Mw.) 19 000 and 110 000 Da. The nanoparticles were characterized by applying dynamic light scattering (DLS), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and Fourier transformed infrared spectroscopy (FTIR). Negatively charged and spherical smooth surfaced nanoparticles of size range between 147-167 nm were obtained. The nanoparticles of monensin-PLGA showed no chemical interaction between monensin and the polymer molecules. The release kinetics in vitro studies exhibited biphasic release profile characterized by an initial fast release followed by a slower release. The antimalarial efficacy of monensin-PLGA nanoparticles was also examined. Monensin loaded in nanoparticles was 10-fold more effective in inhibiting the growth of P. falciparum in vitro as compared to free monensin. The antimalarial efficacy of monensin-PLGA nanoparticles was significantly dependent on the Mw. of the polymer. Copyright © 2012 American Scientific Publishers All rights reserved.