Abstract-This study investigated the effect of low-intensity cathodal direct current on the release of plasma vascular endothelial growth factor (VEGF) and nitric oxide (NO) in diabetic foot ulceration. Twenty type 2 diabetic patients with foot ulceration and thirteen age-matched healthy subjects were enrolled. Patients were randomly assigned to electrical stimulation (ES) (n = 10) or sham ES (placebo, n = 10) groups. The ES group received cathodal direct current (1.48 +/-0.98 mA) for 1 h/d, 3 d/wk for 4 wk (12 sessions). Blood samples were collected for VEGF and NO measurement in the first and last treatment sessions before and after intervention. Wound surface area and skin temperature were measured at the 1st, 6th, and 12th sessions. VEGF significantly increased in the ES group compared with the placebo group after the 1st (106.61 +/-79.50 and 40.88 +/-26.20, respectively) and 12th sessions (109.28 +/-67.30 and 34.79 +/-13.20, respectively). NO level also increased significantly in the ES group compared with the placebo group after the 12th session (44.21 +/-14.00 and 35.25 +/-11.00, respectively). The increase of skin temperature was significantly higher in the ES group than the placebo group. Application of low-intensity ES increases the expression of VEGF and NO, which may lead to improved blood flow and tissue temperature and, consequently, wound healing in diabetic foot ulceration.