To function lipophilic drug Azithromycin (AZM) as ophthalmic preparation, Azithromycin-loaded Nanostructured Lipid Carriers (AZM-NLC) were prepared by High Pressure Homogenization (HPH), and its stability was analyzed afterwards. Well-dissolved lipids of Azithromycin were selected, how the ratio of surfactants to lipids influenced the preparation of AZM-NLC was studied, and mature surfactant system was chosen. The optimized ratio of lipid carriers to emulsifiers [ polyoxyethylene (40) stearate - Poloxamer188 (7:3)] in this study was 1:6, and the final drug-capacity rate was 0.5%. Obtained by photon correlation spectroscopy, the mean particle size of AZM-NLC was 76±2 nm. The results showed that AZM-NLC had kept stable for 15 days, and mean particle size increased to 83 nm after four months.