Abstract: AIM　To investigate the preparation method and the effect of surface modification on the uptake by cells in vitro of stearic acid solid lipid nanoparticles (SLN) surface modified by PEG with different chain-lengths. METHODS　The stearic acid SLN was prepared by the procedure of “emulsification at high temperature (75℃) and then solidified at a low temperature (2℃)”. Three surfactants (Brij 78, Myrj 53 and Myrj 59) with different PEG chains of 1 000, 2 000 and 5 000 in molecular weight were used to modify the surface of SLN respectively. The mouse peritoneal macrophage (MPM) was used to evaluate the uptake of SLN by cells in vitro. RESULTS　The diameters of the three kinds of SLN were (162.0±67.4) nm, (50.2±28.9) nm and (326.8±195.2) nm, respectively. Compared with the (9,10)³H-stearic acid solution, obvious increases of Bq value in MPM were observed by binding (9,10)³H-stearic acid with SLN. The lowest Bq value in MPM was observed in SLN surface-modified by Myrj 59. Protein absorption noticeably increased the uptake of SLN by MPM. CONCLUSION　The results indicate that PEG-coating has obvious effect on the uptake of SLN by MPM: the longer the PEG chain-length, the lower the uptake by cells in vitro.