Sensory abnormality is one of the serious complications in diabetes. Since the effective therapeutic regimen to ameliorate the diabetic sensory abnormality is very few, the present study was then designed to investigate the effect of zinc L-carnosine on the changes of nociceptive threshold in diabetic mice. Zinc L-carnosine (75-300 mg/kg, p.o.) was administered once daily from 1 day after streptozotocin treatment. Diabetic mice showed shorter tail-flick latency at 1-4 weeks after streptozotocin treatment and longer tail-flick latency at 6-9 weeks after its treatment. The shortened tail-flick latency in early stage of diabetic mice was ameliorated by treatment with zinc L-carnosine. Moreover, zinc L-carnosine also slowed the onset of hypoalgesia in diabetic mice. Tail-flick latency in non-diabetic mice was not affected by the zinc L-carnosine treatment, indicating that zinc L-carnosine did not affect normal nociceptive transmission. Moreover, L-carnosine, but not zinc sulfate, ameliorated the abnormal sensory perception in diabetic mice. Interestingly, the ameliorative effect of zinc l-carnosine on the abnormal sensory perception in diabetic mice is much stronger than that of L-carnosine. These results provide the evidence of the ameliorative potential of zinc L-carnosine on the progressive diabetic neuropathy. Moreover, L-carnosine combined with zinc shows more potent amelioration of abnormal sensory perception in diabetic mice than by itself.