Objective To investigate the significance of sympathetic skin response (SSR) in the diagnosis of diabetic small fiber neuropathy. Methods 38 diabetic patients with paraesthesia and 30 healthy controls underwent SSR test on the 4 limbs. The latencies of the initiation and waves N and P of SSR were analyzed. The results of nerve conduction velocities of these patients with paraesthesia were normal. Results The latencies of the initiation and waves N or P in SSR were prolonged in 37 limbs of the 38 patients, and there was no SSR response in 21 limbs. The latencies of the initiation and waves N and P of SSR test in both upper extremity and lower extremities were prolonged significantly in the diabetic patients as compared to the controls (all P＜0. 05). The frequency of abnormality in the latency of SSR was 51% in the lower extremities, and 38% in the upper extremities. The frequency of abnormal latency of SSR in the lower extremities was higher, however, not significantly, than that in the upper extremities (P＞0.05). Twenty-eight of the 38 patients (74%) demonstrated abnormal SSR in at least one limbs. Conclusion SSR can be used to detect the early dysfunction of the small fibers in diabetic peripheral neuropathy, especially in the diabetic patients with normal nerve conduction velocities. SSR test may be a useful and sensitive neuroelectrophysiologic testing for the early diagnosis of diabetic small fiber neuropathy.