OBJECTIVE： To establish the method for the content determination of rapamycin （RAPA） in human monocyte THP-1 derived foam cells， and to study the effects of RAPA targeting preparation （RAPA-NP-Apt） targeting at foam cells. METHODS： Foam cells model were established through THP-1 cells were induced by oxidized low density lipoprotein. Foam cells were incubated with 200 ng/mL RAPA or 200， 400， 800 ng/mL RAPA-NP-Apt for 60 min. The content of RAPA was determined by HPLC. The determination was performed on Diamonsil C18 column with mobile phase consisted of acetonitrile-water （90 ∶ 10， V/V） at flow rate of 1.0 mL/min. The column temperature was set at 40 ℃， and the detection wavelength was 278 nm. The sample size was 20 μL. RESULTS： The concentration of RAPA ranged 50-6 400 ng/mL （r＝0.999 96） with average recovery of 98.72％ （RSD＝0.62％， n＝3）. RSDs of inter-day and intra-day were not more than 6.15％ （n＝6）， RSD of stability was lower than 2％ （n＝6）， and RSD of repeatability was 1.64％ （n＝6）. After foam cells were incubated with RAPA or low-concentration， medium-concentration and high-concentration of RAPA-NP-Apt， the contents of RAPA were 12， 43， 98， 140 ng/106 cells. CONCLUSIONS： The method is simple， stable and reproducible. It can be used for content determination of RAPA in foam cells. RAPA-NP-Apt can improve the effects of RAPA targeting at foam cells.