Background:The most common complication of diabetes mellitus is peripheral diabetic neuropathy associated with neurodegenerative effects. Food and Drug Association approved pregabalin as an anticonvulsant drug, for the treatment of diabetic neuropathy. There were many studies that reported no interest in the effect of this drug because it did not achieve complete recovery of diabetic neuropathy.  So, this study aimed to improve its effect by combining its therapeutic dose with some medicinal plants such as flaxseeds. Materials and Methods:  the experimental animals were divided into five groups. Group I, the control group, was kept without any treatment. Group II administered flaxseed oil (FXO) (1ml/kg body weight/day) for six weeks. A single intraperitoneal dose of alloxan (150 mg/kg b.w.) was used to induce diabetes, then the diabetic animals were divided into the following groups; Group III served as diabetic control. In Group IV the diabetic rats were supplemented with pregabalin (30mg/kg body weight /day) for six weeks. Group V diabetic rats were orally given pregabalin, and after2hours they were given the FXO for six weeks. Results: Diabetes significantly decreased the body weight, superoxide dismutase and catalase activities, and increased the malondialdehyde levels. Microscopic examination of the sciatic nerve of rats showed severe pathological and ultrastructural changes. When diabetic animals were treated with pregabalin only revealed mild improvement that recorded in the biochemical investigation only. However, the sciatic nerve examination of diabetic animals treated with pregabalin and FXO restored the normal histological and ultrastructural pictures and recorded a marked improvement in the biochemical parameters. Conclusion: Flaxseed oil improved the neuroprotective effect of pregabalin against diabetic peripheral neuropathy due to its anti-hyperglycemic, antioxidant and anti-inflammatory properties.