Background <p>Reduced angiogenesis is a key factor in impaired healing diabetic foot ulcers. It is critical to identifying the relevant genes that regulate angiogenesis or the relevant mechanisms that accelerate angiogenesis, which is essential for the treatment of Diabetic foot ulcers (DFU).</p> Methods <p>Direct targeting of miR-125a-5p to Glutathione S-Transferase M5 (GSTM5) was demonstrated by dual luciferase assays. MiR-125a-5p and GSTM5 were induced or silenced by HGM in endothelial cells in vitro, and the results were compared with a blank control to determine the mechanism of miR-125a-5p and GSTM5 expression levels on DFU.</p> Results <p>Initial analysis revealed distinct expression patterns of miR-125a-5p and GSTM5 between acute and chronic DFU patients. Their regulatory roles were investigated by comparing differential expression profiles in these two patient groups. We found that low expression of both in chronic DFU patients was positively correlated with changes in angiogenic markers. Inhibition of miR-125a-5p and GSTM5 in endothelial cells in vitro yielded the same results, demonstrating the promote angiogenesis of their expression on angiogenesis.</p> Conclusion <p>MiR-125a-5p promotes normal angiogenesis in diabetic foot ulcers by targeting GSTM5.</p>