Thiamine supplementation may prevent and reverse early‐stage diabetic nephropathy. This probably occurs by correcting diabetes‐linked increased clearance of thiamine, maintaining activity and expression of thiamine pyrophosphate‐dependent enzymes that help counter the adverse effects of high glucose concentrations—particularly transketolase. Evidence from experimental and clinical studies suggests that metabolism and clearance of thiamine is disturbed in diabetes leading to tissue‐specific thiamine deficiency in the kidney and other sites of development of vascular complications. Thiamine supplementation prevented the development of early‐stage nephropathy in diabetic rats and reversed increased urinary albumin excretion in patients with type 2 diabetes and microalbuminuria in two recent clinical trials. The thiamine monophosphate prodrug, Benfotiamine, whilst preventing early‐stage development of diabetic nephropathy experimentally, has failed to produce similar clinical effect. The probable explanations for this are discussed. Further definitive trials for prevention of progression of early‐stage diabetic nephropathy by thiamine are now required.