Abstract Solid lipid nanoparticles (SLN) were produced using a full range of poloxamer polymers and poloxamine 908 for stabilization. The protein adsorption pattern acquired on the surface of these particles after intravenous injection is the key factor determining the organ distribution. Two-dimensional polyacrylamide gel electrophoresis (2-DE) was employed for determination of particle interactions with human plasma proteins. The objective of this study was to investigate changes in the plasma protein adsorption patterns in the course of variation of the polymers stabilizing the SLN. Considerable differences in the protein adsorption with regard to preferential adsorbed proteins were detected for the different stabilizers. Possible correlations between the polyethylene oxide (PEO) chain length and the adsorption of various proteins (first of all apolipoproteins) are shown and discussed. Besides the study of protein adsorption patterns, the total protein mass adsorbed to the SLN was also evaluated using the bicinchoninic acid (BCA)-protein assay. The knowledge concerning the interactions of proteins and nanoparticles can be used for a rational development of particulate drug carriers. Based on the findings presented in this paper, we anticipate that the in vivo well-tolerable SLN are a promising site-specific drug delivery system for intravenous injection.