Objective To observe the clinical effects of Ziguizhangpi Ointment (ZG) in the treatment of venous leg ulcer (VLU), and to explore the mechanism. Methods Sixty patients with VLU were randomly divided into control group (n=30) and treatment group (n=30). Patients in control group were treated with bovine basic fibroblast growth factor (bFGF), while patients in treatment group were treated with ZG. After 8 weeks of treatment, the clinical effects, wound healing rate and expression of autophagy related proteins (LC3-Ⅱ, beclin-1) in wound granulation tissue were evaluated. Results The total effective rate of the control group was 78.57%, and that of the treatment group was 86.20%. There were statistically significant differences between the two groups (P<0.05);Wound healing rates of the treatment group 6 and 8 months after treatment were both significantly higher than that of the control group (P<0.05);WB showed higher expression of LC3-Ⅱ, beclin-1 in treatment group than in control group (P<0.05). Conclusion In the treatment of VLU, ZG can improve clinical effects, wound healing rate and up-regulate the expression of LC3-Ⅱ, beclin-1 in wound, so as to promote wound healing.