Many studies have examined the role of inflammation in the development of diabetic neuropathy (DPN). Evaluate the relation of the serum level of Transforming Growth Factor-β and Tumor Necrosis Factor-α and development of diabetic peripheral neuropathy DPN. In a case-control study, randomly selected 140 diabetic patients were included, the randomly selected patients were divided equally and matched into a case group who have diabetic peripheral neuropathy and diabetic neuropathy-free patients as a control group. For both groups whole blood sample was examined to compare for (TGF-β), and (TNF-α) levels determination by ELISA technique. The age of the study samples ranged from 25 to 80 years with a male ratio of 1.45:1 although the sex differences between both groups were not significant. The mean levels of (TNF-α) and (TGF-β) was significantly higher among cases group than that of controls group (254.86 ± 75.9 vs158.01 ± 50.600) for TNF-α and for TGF- β (312.85 ± 62.27 vs. 217.82 ± 52.95) respectively. Both TNF-α and TGF-β have high sensitivity and specificity in detection of DPN. The sensitivity of TNF-α was 95.7% and specificity of 61.4% area under the ROC curve (AUC) of 0.870 ± 0.029, while the sensitivity of TGF-β was 91.4%, and specificity of 67.1 with good area under the ROC curve (AUC) of 0.891 ± 0.026 (P=0.000). TNF-α and TGF -β are significantly elevated levels in patients with DPN, these cytokines could be used as indicators for the development of DPN.