This study was designed to investigate the protective effects of Astaxanthin (AST) in rats with diabetes mellitus (DM) induced by streptozotocin. SD rats were divided into control group (n = 5, only received normal saline), DM group (n = 8) and AST + DM group (n = 8; AST: 50 mg/kg/day). DM rats were induced by intraperitoneal injection of streptozocin (STZ, 65 mg/kg). Blood glucose level and body weight were determined at weeks 0, 2, 4, 6 and 8, respectively. At week 8, kidney function was determined, together with expression of P53 and dynamin-related protein-1 (Drp1) by Western blot analysis and immunofluorescence. AST led to increase of body weight in rats with DM. AST + DM group showed a significant decrease in blood glucose level at week 4 compared with DM group (P < 0.05). AST improved renal function and significantly reduced expression of P53 and Drp1 in DM rats. In addition, AST can effectively reduce the blood glucose in DM rats, and delayed the pathogenesis of diabetic nephropathy. Such delay mediated by AST may be associated with the downregulation of Drp1 and P53.