Diabetic neuropathies are a family of nerve disorders caused by diabetes.Symptoms of the disease include nerve palsy,mononeuropathy,mononeuropathy multiplex,diabetic amyotrophy,painful polyneuropathy,autonomic neuropathy,and thoracoabdominal neuropathy.In this study,type 2 diabetes in rats was induced with nicotinamidestreptozotocin.Drug treatment was initiated on the d 15,with the combination regimen of metformin,pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin,amitriptyline and sitagliptin and led to significantly improved glycemic control,increased grip strength and paw jumping response on d 21,28 and 35(P < 0.001).Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21,28 and 35(P < 0.001).Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells,while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain.In conclusion,treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain,but causes an increase in grip strength and pain sensitivity,exhibits neural protection,and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes. Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with diabetes nicotinamidestreptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P <0.001) .Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 (P <0.001) .Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regenerati on and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.