The opsonization or removal of nanoparticulate drug carriers from the body by the reticuloendothelial system (RES) is a major obstacle that hinders the efficiency of the nanoparticulate drug delivery systems. Therefore, several methods of camouflaging or masking nanoparticles (NPs) have been developed to increase their blood circulation half-life. In this study, rhodamine B isothiocyanate (RBITC) loaded NPs were fabricated by an emulsification/solvent diffusion method. The surface of NPs was then modified using either poly ethylene glycol (PEG) or block copolymer of ethylene oxide and propylene oxide, Poloxamer 407 (POL). The surface treatment was carried out using two different methods: (a) co-incorporation of the surface modifying agents (SMAs) into NPs and (b) the external surface adsorptions method and both of these methods were done only by physical incorporation of the SMAs into the NPs, without the need of special chemical reagents. The biodistribution properties of the NPs were then measured. The results confirmed that the surface treatment of the NPs using co-incorporation of the SMAs into NPs is more efficient in increasing the blood circulation half-life of the NPs when compared with the external surface adsorptions method.