Abstract: Objective: To enhance the dispersion of astaxanthin in aqueous phases, astaxanthin-loaded vesicles were fabricated, and their stability under various environmental conditions was examined. Methods: Using unsaturated fatty acid (arachidonic acid) and astaxanthin as raw materials, astaxanthin liposomes were prepared by thin film hydration method. The preparation process of astaxanthin liposomes was optimized through single-factor and response surface experiments, investigating the morphology, particle size and distribution, Zeta potential, encapsulation efficiency, and stability during storage, oxidation, and in vitro digestion. Results: The optimal conditions for preparing astaxanthin liposomes were as follows: Astaxanthin concentration of 0.14 mg/mL, surfactant to fatty acid ratio of 1:1, hydrophilic-lipophilic balance of surfactant of 7, phosphate buffer solution pH of 7.0, and hydration time of 21 min. Under these conditions, the average encapsulation efficiency of astaxanthin liposomes was 89.58%±1.47%. Transmission electron microscopy and particle size analysis showed that astaxanthin liposomes had a spherical structure with an average particle size of (131.74±2.74) nm, a PDI of 0.25±0.01, and a zeta potential of (−38.52±2.31) mV. Stability experiments demonstrated that after 16 days of storage at 4 ℃ in the dark, astaxanthin liposomes showed good stability. The retention rate of astaxanthin in liposomes after freeze-drying and reconstitution was similar to that in liquid state, and they exhibited some tolerance to salt ions. After 16 days of storage, the peroxide value (POV) and TBARS of oil-soluble astaxanthin were twice those of astaxanthin liposomes. After in vitro digestion, the digestibility of astaxanthin in liposomes was 44.19%±2.21% and 74.99%±4.37% at the end of small intestine digestion. Conclusion: The astaxanthin liposomes prepared in this experiment had suitable particle size, good dispersibility, high encapsulation efficiency, and good stability, providing a reference for the development of astaxanthin-derived products.