The key findings of this study are summarized as follows: (1) serum ANGPTL2 levels were higher in the DFU group compared with the control (T2DM); (2) serum ANGPTL2 levels were higher in the advanced stages of DFU; (3) serum CRP, ESR, and VEGF levels were increased in the presence of DFUs; (4) serum ANGPTL2 levels were significantly positively related to CRP, ESR, and VEGF levels, individually; (5) serum ANGPTL2 was positively correlated with diabetic foot stage after adjusting the risk factors; (6) ANGPTL2 was demonstrated to be an independent risk factor for DFUs. This evidence concerns the gene ANGPTL2 and type 2 diabetes mellitus.