To study the role of tumour necrosis factors-alpha (TNF-alpha) in mechanical hyperalgesia in type-2- diabetic rat, diabetic mechanical hyperalgesia model was established in female Wister rats by combining high-fat diet for 4 weeks and single intraperitoneal injection of streptozotocin (STZ, 30 mg/kg, serum glucose increased from 12.7 ± 0.44 mmol/L to 28.3 ± 0.59 mmol/L after STZ injection). Based on hyperalgesia symptoms, rats were divided into hyperalgesia group (HFDH) and non-hyperalgesia group (HFDNH). Hyperalgesia rats were further treated with or with TNF-alpha inhibitor (HFDHTNFI). Compared with HFDNH group, hyperalgesia symptom was evident in HFDH rats in that PWT is 26 ± 0 g HFDNH group and 7.371 ± 1.49 g in HFDH respectively. On the other hand, serum level of TNF-alpha was lower in HFDH rats (76.64 ± 3.40 pg/ml) than those in HFDNH rats (109.7 ± 6.23 pg/ml). Sensitization of hyperalgesia and low serum TNF-alpha in HFDH group could be restored by TNF-alpha inhibitor (serum TNF-alpha was 106.1 ± 2.39 pg/ml and PWT was 26 ± 0 g after TNF-alpha application). Thus down-regulation of serum TNF-alpha is involved in progression of type2-diabetic mechanical hyperalgesia.