Abstract: OBJECTIVE To prepare imiquimod(Imiq) liposomes using pH gradient active drug loading technology based on the physicochemical properties of Imiq, and investigate the characters, particle size, surface charge and release characteristics in vitro. METHODS To determine the encapsulation efficiency by gel filtration method, and use encapsulation efficiency and formability as the main index of preparation screening. To study the impact on entrapment efficiency of the factors involving hydration liquid type, pH value, ionic strength and pH gradient drug loading, phospholipid and cholesterol ratio, drug lipid ratio and the dosage of VE. To optimize the prescription composition of imiquimod liposomes by orthogonal test prescription, and then to observe the stability of liposome samples at 0-4℃. RESULTS The prescription composition of imiquimod liposomes were 50 mg of Imiq, 400 mg of soybean soft phospholipid, 130 mg of cholestorol, 10 mg of oleic acid, 5 mg of vitamin E, 5 mL of citric acid pH 2.5 buffer, and use THF-pH gradient active loading technology, the pH value was adjusted to 7.0. The prepared Imiq liposomes showed white uniform suspension, had round and well dispersed particles, and the particle size was (347±21)nm, encapsulation efficiency was (81.2±1.9)%, Zeta potential was (-12.19±1.7)mV. CONCLUSION The pH gradient active drug delivery technique is suitable for the preparation of Imiq liposomes.