Astaxanthin (AX) is a natural compound that regulates lipid metabolism in the liver, specifically in reducing hepatosteatosis. To the increment in Non-Alcoholic Fatty Liver Diseases (NAFLD) ratio and its burdens, prevention/treatment should address the world health problem. This study aimed to evaluate the ability of AX and its prolonged effects on the physiology of mice fed a high-fat diet. Mice fed with a high-fat diet (HFD) (n=12) were orally given AX at a dosage of 30 mg/kg body weight/day for 16 weeks, followed by eight weeks of AX termination, along with other CTL (normal chow diet) and HFD only group. At four time points of 8, 12, 16, and 24 weeks of the trial, three mice from each group were randomly dissected to collect blood, liver, and adipose tissue samples. AX given through oral gavage showed an excellent factor for maintaining total cholesterol, triglyceride, glucose, and Low-density Lipoprotein cholesterol (LDL-c). Moreover, AX did have impacts on preventing dyslipidemia in mice fed with HFD. Unexpectedly, AX supplied group caused excess weight gain in mice, shown in higher average body weight than HFD fed group. However, all the AX effects wore off after 8 weeks of termination. AX was a good player for liver and plasma lipid homeostasis, but not for weight control. Taken together, AX was a potential compound for preventing hepatosteatosis and hyperlipidemia, but not for controlling weight in mice fed with a HFD.