Neuropathy is one of the complications of diabetes which alters structure and function of the basement membranes in nerves. Collagen IV is the most prominent component of basement membranes in sciatic nerve. We examined the effects of α-lipoic acid (ALA), as an antioxidant agent, on blood glucose levels, body weight and alterations in collagen IV expression of sciatic nerve in the diabetic rats. Diabetes was induced in the rats by intraperitoneal injection of streptozotocin (55 mg/kg). After 12 weeks of diabetes, collagen IV expression in sciatic nerves was evaluated by immunohistochemical study and real time polymerase chain reaction (PCR). Our findings revealed that ALA treatment significantly decreased blood glucose levels in the diabetic rats but did not significantly affect the body weight. Collagen IV immunoreactivity was stronger in the perineurium, endoneurium and blood vessels basement membrane of sciatic nerve in untreated diabetic rats compared to control group. ALA treatment significantly decreased collagen IV expression only in the basement membrane of blood vessels. Collagen IV mRNA level of sciatic nerve in untreated diabetic rats significantly increased compared to control group. ALA failed to protect sciatic nerves against collagen IV mRNA up-regulation. We suggest that ALA has the potential in improving hyperglycemia by reducing oxidative stress and may partially prevent collagen IV alteration in sciatic nerves.