Objection: Neuropathy is the most common and debilitating complication of diabetes. Microvascular endothelial dysfunction plays an important role in the development of the neuropathy. To prevent the severe consequence, a test for early diagnosis of the disease is urgent. Here we studied the structure and function changes of microvascular endothelium cells and skin small nerve fibers changes in type 2 diabetes patients, to discuss the relationship between microvascular disorders and peripheral nerves changes. We also compared the clinical, electrophysiologic and skin small fiber pathologic features in type 2 daibetes patients, in order to establish a diagnostic way for diabetic neuropathy in early stage. Material and methods: 5 male patients who were diagnosed as diabetic neuropathy and done sural nerve biopsy in our department from 2003 to 2008 were reviewed. All the 5 patients suffered from numbness and/or pian of both lower limbs and showed decrease of nerve conduction velocity (NCV) and/or amplitude of nerve action potential (NAP). 16 type 2 diabetes patients were collected. All the 16 patients were screened by MNSI score and separated into 3 groups – non neuropathy, mild neuropathy and moderate neuropathy - by the scores. They were all examed with NCV and SSR. Decrease of nerve conduction velocity (NCV) and/or amplitude of nerve action potential (NAP) was detected in 11 cases, and the evoke potential of SSR was not educed in 13 caes. The routine histopathology, the ultramicropathology and the immunohistopathology were detected on the 5 nerve biopsy samples. The primary antibodies Von Willebrand Factor (VWF), endothelial nitric oxide synthase (eNOS) and thrombomodulin(TM) were used by immunohistochemistry staining. The routine histology and immunohistochemistry staining was done on the 16 skin biopsy samples. The primary antibodies for detecting vascular were CD 31, eNOS and TM, for skin small nerve fibers was protein gene product 9.5 (PGP 9.5). Results: The reduction of myelinated fibers in fasciculus, endothelial cells hyperplasia, thinkening of basement menberens were detected in all sural nerve sections. The expression of eNOS and TM on the microvascular endothelial cells was decreased in all the 5 cases. The blood vessel dencity of skin was increased. The expression of eNOS and TM on the microvascular endothelial cells was also decreased in all the skin section. Intraepidderaml nerve fiber dencity (IENFD) was decresed in 13 cases, normal range in 2 case and increased in 1 case. With increasing severity of neuropathy, IENFD showed a progressive reduction while blood vessel dencity and HbA1C showed progressive increase, all of which are significant in patients with moderate neuropathy. IENFD correlated negatively with HbA1C, which is statistically significant. Conclusion: The structure and function of microvascular was changed in diabetes patients. The reduction of vasodilatory and anti-thrombosis ability of microcirculation may induce the nerve lesions. Immunostaining for intraepidermal nerve fibers was a useful method to diagnose diabetic neuropathy in early stage.