OBJECTIVE： To optimize the preparation technology of Norfloxacin solid lipid nanoparticles and investigate its drug release characteristics in vitro. METHODS： The content of norfloxacin was determined by UV spectrophotometry. Norfloxacin solid lipid nanoparticles were prepared by ultrasound-high pressure homogenization. Using encapsulation rate and particle size as indexes， single factor tests of preparation technology were conducted by using the scoring method， and the Box-Behnken response surface method was used for optimization. TEM was used to observe its morphology of Norfloxacin solid lipid nanoparticles. The release characteristics were investigated by release test in vitro. RESULTS： The linear range of norfloxacin were 0.2-1.2 μg/mL （r＝0.999 5）. The optimal technology was glycerol tristearate as lipid material， fabaceous lecithin： poloxamer 188 （1 ∶ 2，m/m） as surfactant， shearing velocity of 15 000 r/min， lipid-drug ratio of 7.67 ∶ 1， drug concentration of 8.91 mg/mL， ultrasonic time of 4.80 min， ultrasonic temperature of 65 ℃， homogeneous pressure of 120 MPa， freeze-dried protective agents of 10％ trehalose. Norfloxacin solid lipid nanoparticles were nearly spherical in shape and uniform in size with average particle size of （168.0±4.8） nm. Average encapsulation rate was （86.8±5.1）％； burst release appeared within 1 h， and accumulative release rate was （75.7±8.1）％ within 8 h. CONCLUSIONS： The prepared Norfloxacin solid lipid nanoparticles have good shape， suitable particle size and good sustained-release characteristics in vitro.