Abstract: Liposomes are vesicle-shaped particles whose walls are composed of lipid molecules ( the main constituent is a double layer phospholipid which wraps the liquid compartment inside. Liposomes can be made from natural ingredients in the form of natural phospholipid derivatives mixed with fat chains (eg phosphatidylcholine) by dispersing. Liposomes from papaya leaf extract (Carica Papaya Linn) are made with the aim of increasing the effectiveness of the drug and biocompatible work, as well as protecting healthy tissue from the toxic effects of the drug. The process of making liposom papaya leaf extract using the sonication method by mixing soybean lecithin with papaya leaf extract. Then do the heating and sonication. This method is done to reduce particle size. The aim of this study was to produce an extract of liposomes from papaya leaf phospholipid formulations using a combination of heating and sonication. The method to produce liposomes with a size of <150 nm using a combination of heating 40○C for 40 minutes and stirring using ultraturrax at a speed of 15,000 rpm for 30 minutes, then stirring with a sonicator for 30 minutes. The results showed the liposome nano papaya leaf extract formulation from soybean lecithin by the PSA (Particle Size Analyzertype 1090 / Cilas) method. The liposome product was in the form of liquid, light green and milk white and odorless. Particle size distribution is obtained in the range of 0.04 µm - 500.00 µm / 100 Classes and an average pH of 5.45.