Objective To investigate the changes of transforming growth factor β1 (TGF- β1) and type Ⅱ of TGF-β-receptor (TβRⅡ) expressions in wound tissue after the treatment of diabetic foot with vaccum sealing drainage (VSD), and to analyze the mechanism of accelerating wound healing. Methods Between May 2012 and May 2016, 80 patients with diabetic foot were randomly divided into 2 groups, 40 cases in each group. After the same basic treatment, the wounds of VSD group and control group were treated with VSD and external dressing, respectively. There was no significant difference in gender, age, disease duration, body mass, foot ulcer area, and Wagner grade between 2 groups (P>0.05). The time of foundation preparation and hospitalization stay of 2 groups were recorded. The wound tissue was collected before treatment and at 7 days after treatment, and the positive indexes of TGF-β1 and TβRⅡexpressions were measured by immunohistochemical staining. Results Before skin grafting, the patients in VSD group were treated with VSD for 1 to 3 times (mean, 2 times), and the patients in control group were treated with dressing change for 1 to 6 times (mean, 4 times). The time of foundation preparation and hospitalization stay in VSD group were significantly shorter than those in control group (t=–13.546, P=0.036; t=–12.831, P=0.041). The skin grafts of both groups survived smoothly and the wound healed well. Before treatment, immunohistochemical staining results showed that the positive indexes of TGF-β1 and TβRⅡ expressions in VSD group were 5.3±2.4 and 14.0±2.6, while those in control group were 4.4±2.3 and 14.7±3.1, respectively. There was no significant difference between 2 groups (t=1.137, P=0.263; t=1.231, P=0.409). At 7 days after treatment, the positive indexes of TGF-β1 and TβRⅡ expressions in VSD group were 34.3±2.9 and 41.7±3.7, respectively, and those in control group were 5.8±2.0 and 18.1±2.5. There were significant differences between 2 groups (t=–35.615, P=0.003; t=23.725, P=0.002). Conclusion VSD can increase the expressions of TGF-β1 and TβRⅡ in diabetic ulcer tissue, promote granulation tissue growth, and accelerate wound healing.