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Astaxanthin (Ast) has been reported to reduce oxidative stress induced by diabetes mellitus (DM). The aim of this research was to give a systematic overview of the biological basis for this process. Ast-targeted proteins were collected from the BATMAN database, Comparative Toxicogenomics Database, and STITCH database. Putative DM-related protein targets were collected from the GeneCards database. A DM-rat model was then built with streptozotocin (STZ) combined with a high-sugar, high-fat diet for 30 days. Total cholesterol (TC), trigly