Background: Diabetic nephropathy is a major health concern. Astaxanthin (ASX) has antioxidant and anti-inflammatory impacts. Objective: To illustrate the reno protective impact of ASX in STZ induced diabetic nephropathy and the underling mechanisms involved. Material & methods: Thirty Wister albino male rats divided into control, DN, DN+ASX groups. After 8 weeks serum levels of glucose, glycosylated Hb A1_c, urea, creatinine, cystatin C in addition to creatinine clearance, urinary albumin, renal MDA, SOD TNF-α, IL-6, caspase-3, Renal genes HMGB1, TLR4 and NF‑κB were assessed. Histopathological assessment of renal tissue was done. Results: Serum levels of glucose, glycosylated Hb A1_c, urea, creatinine, cystatin C in addition to urinary albumin, renal MDA, renal TNF-α, renal IL-6, renal caspase-3, renal HMGB1, TLR4 and NF‑κB gene expression of DN group were significantly increased compared to control however renal SOD and creatinine clearance values of DN group were significantly decreased compared to control. ASX dramatically improved diabetic nephropathy induced changes. Conclusion: ASX alleviated diabetic nephropathy induced changes by anti-oxidant, anti-inflammatory, anti-apoptotic mechanisms and modulating HMGB1, TLR4 and NF‑κB renal genes expression.