Diabetic neuropathic pain, an important microvascular complication of diabetes mellitus is recognized as one of the most difficult types of pain to treat. The development of tolerance, inadequate relief and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of lycopene and its effect on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) release in streptozotocin induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia alongwith increased plasma glucose and decreased body weights as compared with control mice. Lycopene (1, 2 and 4 mg/kg body weight; per oral) treatment, from the 4th to 8th week after streptozotocin injection, significantly attenuated thermal hyperalgesia and the hot-plate latencies. Lycopene also inhibited the TNF-alpha and NO release in a dose dependent manner. These results indicate an antinociceptive activity of lycopene possibly through its inhibitory action on NO and TNF-alpha release and point towards its potential to attenuate diabetic neuropathic pain.