Objective To explore the effects of salidroside ( SAL) on nuclear transcription factor-E2 related factor 2 / Kelch-like epichlorohydrin-related protein 1 ( Nrf2 / Keap1) signaling pathway and wound healing in rats with diabetic foot ulcer (DFU). Methods Diabetes was induced in rats by feeding of a high-fat and high-glucose diet and intraperitoneal injecting of streptozotocin (STZ), and the back of the foot was shaved and cut to the fascia to create an ulcer wound with an area of approximately 3 mm×7 mm to establish DFU rat model. The rats were randomly allocated to a DFU model group; Sal-L (0. 1 g(kg·d)), Sal-M (0. 2 g / (kg·d)), Sal-H (0. 3 g( kg·d)) groups, metformin group (MET, 0. 65 g / (kg·d)), and set normal blood glucose wound rats as the control group (NC group), and all were gavaged daily for 2 weeks. The body mass and concentration of fasting-blood glucose (FBG) of all the rats were measured on the 7th and 14th days of treatment; the expression of CD34 was assessed by immunohistochemistry; the microvascular density (MVD) of the wounds was calculated; the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) concentrations were measured biochemically, and the expression of Nrf2 and Keap1 proteins in the wound tissue was measured by Western blot. Results Prior to the start of treatment, there was no significant difference in the body masse between the groups, while the FBG of the DFU, Sal-L, Sal-M, Sal-H, and MET groups was higher than that of the NC group (P<0. 05). On the 7th and 14th day of treatment, the body mass, FBG, MDA content, and Keap1 protein expression in the DFU, Sal-L, Sal-M, Sal- H, and MET groups were higher than those in the NC group (P<0. 05); and the wound healing rate, CD34 positive cells, MVD, SOD activity, and Nrf2 protein expression were significantly lower (P<0. 05). The body mass, FBG, MDA content, and Keap1 protein expression in the Sal-L, Sal-M, Sal-H, and MET groups were lower than those in the DFU group (P< 0. 05); and the wound healing rate, CD34 positive cells, MVD, SOD activity, and Nrf2 protein expression were significantly higher (P<0. 05). However, there were no significant differences between the Sal-L and MET groups (P> 0. 05). Conclusions Sal may increase the antioxidant capacity and promote wound healing in rats with DFU via the Nrf2 / Keap1 signaling pathway.