The lyophilized solid lipid nanoparticles (SLN) loaded with all-trans retinoic acid were prepared using different cryoprotectants. The effects of different cryoprotectants on the properties of SLN such as appearance, the mean particle size and encapsulation efficiency after lyophilization and reconstitution were investigated to optimize the combination of cryoprotectants. The results showed that using sucrose alone or the combination of different cryoprotectants e.g. sucrose and trehalose, mannitol and trehalose or mannitol and sucrose, the mean size and the encapsulation efficiency of the lyophilized products after reconstitution decreased by comparison with those of the products before lyophilization. Trehalose formulation offered a rapid hydration velocity. The freeze-dried SLN displayed good stability after storage for 3 months at 4℃ and 20℃.