OBJECTIVE： To prepare rifampicin （RFP） nano-structured lipid carriers （RFP-NLCs） to improve its water-solubility， and evaluate its quality. METHODS： Using liquid-solid lipid materials oleate and glyceryl monostearate as lipid materials， soy lecithin as emulsifier， poloxamer 188 as nonionic surfactant， melting-ultrasonic emulsification was used to prepare RFP-NLCs. Using the comprehensive scores of particle size and encapsulation efficiency as indexes， the amount of lipid materials， proportion of liquid lipid materials， dosage， and mass ratio of soy lecithin-poloxamer 188 as factors， orthogonal test was adopted to optimize the formulation. The morphology， particle size， polydispersity index （PDI）， Zeta potential， encapsulation efficiency， drug loading and in vitro release degree of prepared lipid carriers with optimal formulation were evaluated. RESULTS： In the optimal formulation， the amount of lipid materials was 150 mg， proportion of liquid lipid materials was 30％， amount of RFP was 10 mg， and mass ratio of soy lecithin-poloxamer 188 was 1 ∶ 3. Prepared RFP-NLCs had rounded appearance， particle size was （124.07±3.25） nm， PDI was 0.104±0.010， Zeta potential was （－31.07±2.94） mV， encapsulation efficiency was （80.90±2.59）％， and drug loading was （4.81±0.68）％ （n＝3）. Compared with RFP raw materials， in vitro release degree of RFP-NLCs significantly slowed down， and the cumulative release degree within 12 h was 63.2％， which was in line with Weibull equation. CONCLUSIONS： Screened formulation can successfully prepare RFP-NLCs； the prepared RFP-NLCs have small particle size and high encapsulation efficiency， and the in vitro drug release shows certain sustained-release characteristics.