ABSTRACT Background: Calprotectin was identified as an endogenous activator of Toll-like receptor 4 (TLR4) and as receptor for advanced glycation end product (RAGE). Elevated plasma levels of calprotectin have been reported in a variety of chronic inflammatory conditions. Elevated calprotectin levels have been reported to predict microvascular alterations in type 2 diabetes (T2DM) patients. Objective: To make an up to date review of serum level of calprotectin as a predictor for early diagnosis of peripheral neuropathy in type 2 diabetes patients. Patients and methods: A total number of 90 subjects were included in the study after fulfillment of the inclusion and exclusion criteria. Calprotectin was measured for all the 90 subjects. Results: Serum calprotectin levels were significantly higher in group III “diabetics with neuropathy” compared to group II “diabetics without neuropathy “and group I “healthy controls”. Conclusion: High levels of calprotectin were detected in type 2 diabetic patients with peripheral neuropathy. Keywords: Calprotectin, Diabetes mellitus, Neuroinflammation, Peripheral neuropathy.