Introduction. Maintaining adequate skin hydration is crucial in the feet of patients with diabetes because xerotic skin may crack and develop fissures, thereby increasing vulnerability to ulceration and infection. The nervous system is considered the powerhouse for maintaining adequate skin hydration; however, no clinical study has assessed the effect of the nervous system on skin hydration. In addition, it is hypothesized that microcirculation may play an important role in maintaining adequate hydration in patients with diabetes. Objective. This study aims to evaluate the influence of peripheral nerve function and microvascularity on skin hydration in the feet of patients with diabetes mellitus and compare the effects of these 2 functions on skin hydration. Materials and Methods. This study included 266 patients with diabetic foot disease. Skin hydration was evaluated using corneometry and microvascularity by measuring the transcutaneous oximetry (TcpO₂) of the foot. The Semmes-Weinstein 5.07/10-g monofilament test, electromyography, and nerve conduction velocity test were conducted to evaluate peripheral neuropathy. Patient data were divided into 3 subgroups according to test values, and statistical comparisons were performed using the linear-by-linear association trend and Pearson’s chi-square tests. Results. There was a significant (P < .001) correlation between skin hydration and TcpO₂. However, there was no significant correlation between skin hydration and peripheral nerve function (P = .338). Conclusions. The results of this study demonstrated that skin hydration in the feet of patients with diabetes mellitus mainly is influenced by microcirculation rather than peripheral nerve function.