OBJECTIVE This study is aimed to investigate whether there are any histopathological differences between diabetic and idiopathic carpal tunnel syndromes. METHODS The biopsy specimens were taken from transverse carpal ligament (TCL), tenosynovium adjacent to median nerve and epineurium of median nerve and evaluated in 47 patients (21 diabetic and 26 idiopathic) who were diagnosed with carpal tunnel syndrome (CTS) and treated surgically with open carpal tunnel release. Fibroblast proliferation, fibrosis, perivascular inflammation, oedema, vascular proliferation and vascular wall thickness were determined and scored in all specimens. RESULTS There weren't any histopathological abnormalities in TCL specimens of both groups. Synovial hyperplasia, fibrosis and perivascular inflammation were not observed in tenosynovial analysis of both groups. Diabetic CTS patients, when compared with idiopathic CTS patients, had higher rates of synovial edema (idiopathic CTS 57 %, diabetic CTS 87 %), vascular proliferation (idiopathic CTS 30.8 %, diabetic CTS 90.5 %) and increased vascular wall thickness (idiopathic CTS 11.5 %, diabetic CTS 90.5 %). There was no oedema, fibrosis and perivascular inflammation of the epineurium in specimens of either group. But increases in vascular proliferation (idiopathic CTS 7.7 %, diabetic CTS 71.4 %) and vascular wall thickness (idiopathic CTS 3.8 %, diabetic CTS 71.4 %) was seen in the epineurium of diabetic patients and these differences were statistically significant (p < 0.05). CONCLUSIONS Because of the severe synovial and epineurial histopathological abnormalities and inadequate neural regeneration capacity, surgical open carpal tunnel decompression should be planned earlier in diabetic CTS patients. Further studies should be considered to evaluate the histopathological features of diabetic CTS patients early in the course of the disease.