OBJECTIVE： To optimize the formulation of indomethacin-loading solid lipid nanoparticle （SLN）. METHODS： Using indomethacin as model drug， glyceryl behenate as oil phase， poloxamer 188 and polyethylene glycol-12-hydroxystearic acid as emulsifier， with turbidity， entrapment efficiency and drug loading amount as index， Box-Behnken response surface methodology was used to optimize the amount of oil phase， emulsifier-oil phase ratio， drug-oil phase ratio. The physicochemical properties of SLNs were characterized by SEM and DSC. RESULTS： The optimal formulation was as follows as oil phase of 0.91％， emulsifier- oil ratio of 1 ∶ 1， drug-oil phase ratio of 1 ∶ 5. The turbidity， entrapment efficiency and drug loading amount of prepared nanoparticle were 1 025-1 030 NTU， 98.94％-99.08％， 2.43％-2.46％， respectively； particle size and polydispersity index （PDI） were 181.5- 182.3 nm and 0.340-0.341 （n＝3）. The results of DSC showed that indomethacin was not present in crystalline state dispersed into SLNs. CONCLUSIONS： The optimal formulation is screened successfully， and indomethacin-loaded SLNs have been prepared.