Aldose reductase inhibitors (ARIs) hold great promise as an important therapeutic class in the management of diabetic neuropathy.One important metabolic factor underlying diabetic neuropathy is an enhanced polyol pathway.ARIs suppress the activity of aldose reductase, a rate-limiting enzyme involved in the polyol pathway.Currently, Epalrestat is the only ARI available commercially in Asia.Several published reports have described the efficacy and safety of Epalrestat in management of diabetic neuropathy.Methylcobalamin, the neurologically active form of vitamin B 12 enhances nerve regeneration in neuropathies.Over the years, Methylcobalamin is rapidly gaining clinical acceptance in management of diabetic neuropathy.The efficacy and safety of Epalrestat and Methylcobalamin alone or in combination was evaluated in two separate clinical studies conducted in patients with diabetic neuropathy in India.1) A prospective, open-labeled, comparative, multicentric study was conducted to compare the efficacy, safety, and tolerability of Epalrestat with Methylcobalamin in 242 patients for a 12-week treatment period.Epalrestat demonstrated better efficacy than Methylcobalamin.2) A phase Ⅲ, single-blind, randomized, comparative, multicentric, 12-week study conducted in 220 patients to evaluate efficacy and safety of Epalrestat and Methylcobalamin combination with Epalrestat alone concluded that combination of Epalrestat and Methylcobalamin showed better improvement in neuropathic symptoms and tendon reflex, higher reduction in mean pain intensity score, improvement in muscle strength score in more number of patients as compared with Epalrestat alone.Both treatments were well tolerated and there were no serious adverse events observed in both the studies.In conclusion, Epalrestat would be a useful therapeutic option to prevent or slow the progression of diabetic neuropathy.Further, combination of Epalrestat and Methylcobalamin emerges as a better and more effective approach in treating diabetic neuropathy than Epalrestat alone.