Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide (As₂O₃) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As (iAs^III) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by As₂O₃ exposure ( via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, Na⁺-K⁺ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of As₂O₃ exposure. AST showed a significant protective effect against As₂O₃-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to iAs^III from natural sources or cancer therapy.