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Astaxanthin-loaded liposomes were prepared by employing a thin-film ultrasound method with the utilization of soy phosphatidylcholine. The preparation conditions of astaxanthin-loaded liposomes were optimized through response surface methodology. Under the optimum preparation conditions, the observed experimental results showed the vesicle size of astaxanthin-LL was 80.62 ± 4.52 nm with the polydispersity index of 0.20 ± 0.03, while the zeta potential was −31.80 ± 1.85 mV with the highest encapsulation efficiency of 97.68 ± 0.34%. The successful encapsulation of astaxanthin in liposomes was demonstrated by Fourier-transform infrared spectroscopy. Retention rate of 82.29% was obtained after 15 days of storage at 4°C in the stability study, which confirmed that the liposome membrane could retain astaxanthin effectively, especially at low storage temperature. Encapsulation could enhance significantly the antioxidant activity of astaxanthin. Additionally, the antioxidant activity of astaxanthin after encapsulation in liposomes was correlated with the incorporation efficiency of astaxanthin.