Diabetic neuropathy is associated with changes in composition of extracellular matrix. Laminin is a major component of extracellular matrix. In this study, we investigated protective effects of insulin and alpha lipoic acid on improving of blood glucose levels, body weight and laminin expression of sciatic nerve in diabetic rats. Diabetes was induced in the rats by 55 mg/kg streptozotocin (STZ) via an intraperitoneal injection. 12 weeks after STZ treatment, laminin expression in sciatic nerves was evaluated by immunohistochemical study and real time polymerase chain reaction. Laminin expression increased in the perineurium, endoneurium and blood vessels walls in sciatic nerve of untreated diabetic rats compared to control rats. Insulin treatment significantly reduced overall laminin immunoreactivity but alpha lipoic acid treatment significantly decreased it only in the blood vessels walls. Laminin β1 mRNA level in sciatic nerve of untreated diabetic group increased 0.6 fold compared to control group. Although, alpha lipoic acid decreased this up regulation but unlike insulin, this reduction was not significant. These findings suggest that untreated diabetic neuropathy in rats might be associated with increased laminin expression and also it implies that insulin therapy is more effective than alpha lipoic acid treatment in improving hyperglycemia and laminin up-regulation in diabetic nerves.