OBJECTIVES: To assess the effects of heparin and heparin-related substances for the treatment of foot ulcers in diabetes mellitus. METHODS: In June 2015 we searched: The Cochrane Central Register of Controlled Trials; Ovid MEDLINE;Ovid EMBASE; EBSCO CINAHL; Chinese Biomedical Literature Database; VIP Chinese Science and Technique Journals Database; China National Knowledge Infrastructure Database and Wan Fang database.Studies involving people with type 1 or type 2 DM with foot ulcers, comparing heparin and heparin-related substances with placebo or conventional therapy.Two review authors independently extracted data and assessed risk of bias. Any disagreements were resolved through discussion. We assessed each included study based on the Cochrane Collaboration risk of bias tool. RESULTS: We included 10 randomised studies.Two different heparin and heparin-related substances were evaluated in the included trials, which compared low-molecular-weight heparin (LMWH) or hyaluronic acid with conventional therapy. All the included trials reported that they use random methods when they recruited participants for different intervention groups. Compared to conventional therapy the results showed that hyaluronic acid may promote the healing completely of diabetic foot ulcers (RR 1.45, 95%CI 1.17 to 1.79). Three studiesinvestigated LMWH versus conventional therapy and reported improvements in the complete healing rate of diabetic foot ulcers (RR 1.31, 95%CI 0.83 to 2.06). The rates of total adverse events and the rates of serious adverse events were similar in heparin or a related substance group and the conventional therapy group. CONCLUSIONS: Current evidence suggests that hyaluronic acid could be considered as a potential beneficial therapy for promoting the healing of diabetic foot ulcers compared with conventional therapy. It would not be appropriate to give any practical advice for the use of the LMWHs. However, all included studies were small. Thus further larger studies with larger and longer follow-up are needed.