Astaxanthin (ASTA), a natural pigment carotenoid, is endowed with remarkable antioxidant activity in food and cosmetic products. However, the utilization of ASTA is limited due to its poor water-solubility, low bioavailability, and the decomposition under light, heat, and oxygen. In order to overcome these drawbacks, ASTA was encapsulated within solid lipid nanoparticles (SLNs). ASTA-SLNs, composed of lipid nucleation (ASTA, soybean oil, solid lipid matrix) and external water phase (Tween 20, deionized water), were prepared by high pressure homogenization (HPH). The contents of three different solid matrixes (stearic acid, glycerin monostearate, and glycerol distearates) and the preparation conditions (pressure and number of cycles) were optimized. Stearic acid (1 wt%) was selected on the basis of physico-chemical properties of ASTA-SLNs, such as mean particle size, zeta potential, and polydispersivity index (PDI). Moreover, ASTA-SLNs exhibited good long-term stability at 4 and 25°C, with no significant modification in the particle size. Comparative with the free ASTA, the chemical stability of ASTA in SLNs was significantly enhanced. Finally, the release experiments of ASTA-SLNs showed that SLNs could provide prolonged release of ASTA in simulated gastric and intestinal juices.Practical application: SLNs, a promising submicron drug delivery system, could be widely applied in food, cosmetics, drugs, and health products. In the fields of targeted delivery and controlled release of drugs, SLNs have attracted increasing attention. ASTA-SLNs can be prepared into various pharmaceutical dosage forms, such as oral tablet, intravenous infusion, and percutaneous absorption, thus achieving a long-time and stable therapeutic effect in small dosage. More importantly, based on the high pressure homogenization technology, ASTA-SLNs can be produced in large-scale.