Astaxanthin is a carotenoid with powerful antioxidant properties that exists naturally in various plants, algae, and seafood. The purpose of the present study is to examine the protective action of astaxanthin against high-glucose-induced oxidative stress, inflammation, and apoptosis in proximal tubular epithelial cells (PTECs). To assess the efficacy of astaxanthin, several key markers and activities were measured, including lipid peroxidation, total reactive species (RS), superoxide (*O(2)), nitric oxide (NO*), and peroxynitrite (ONOO(-)), as well as expressions of inflammatory proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-kappaB) nuclear translocation, and levels of Bcl2/Bax protein. Results showed that astaxanthin effectively suppressed lipid peroxidation, total RS, *O(2), NO*, ONOO(-), iNOS and COX-2 protein levels, NF-kappaB nuclear translocation, and pro-apototic Bax, whereas it increased anti-apoptotic Bcl2 protein levels. On the basis of these findings, it was concluded that in PTECs, astaxanthin has a protective efficacy against several deleterious effects caused by high glucose exposure and proposed that astaxanthin should be explored further as a potential antidiabetic remedy for the treatment of diabetic nephropathy.