The aim of the present study was to explore the effect of rutin on early diabetic neuropathy in experimental animals. Streptozotocin (55 mg/kg, i.p.) was administered to different groups of rats. Four weeks after injection of streptozotocin, rutin (50 and 100 mg/kg, p.o.), metformin (200 mg/kg, p.o.) and sertraline (30 mg/kg, p.o.) were administered in diabetic rats (n=5) for three weeks. The antidiabetic activity of rutin was studied by measuring serum glucose, serum triglyceride and glycosylated hemoglobin. Thermal hyperalgesia, formalin induced hyperalgesia, cold allodynia, walking function test, tumour necrosis factor- alpha, plasma antioxidant enzymes like SOD, NO, MDA, GSH, catalase levels and sciatic nerve axonal degeneration were performed to assess the extent of neuropathy. Four weeks after a single dose intraperitoneal injection of streptozotocin (55 mg/kg), rats exhibited significant hyperalgesia along with increased serum glucose and decreased body weights as compared with control rats. Treatment of rutin (50 and 100 mg/kg; p.o.) given for 3 weeks starting from the 4th week of streptozotocin injection significantly lowered biochemical changes and delayed paw and tail withdrawal latency in hyperalgesia and allodynia respectively. Preventive treatment of rutin significantly improved paw flinching response in formalin induced hyperalgesia. Rutin also inhibited the level of serum TNF-α. Rutin restored antioxidant enzymes NO level and SOD, GSH, CAT level activities in diabetic rats. Rutin has shown beneficial effect in preventing the progression of early diabetic neuropathy in rats.