Objective To identify the risk factors for the occurrence and development of diabetic foot(DF) in patients with type 2 diabetes mellitus, and to study the influence of blood glucose fluctuation on DF. Methods Clinical data of 192 patients with non-DF and 575 patients with DF were analyzed. According to the severity of DF, 575 DF patients were further divided into Wagner 1~2, Wagner 3, and Wagner 4~5 subgroups. According to whether amputation was performed or not, 575 patients with DF were further divided into DF with amputation and without amputation groups. The analysis factors included biochemical indicators, standard of blood glucose (SDBG), coefficient of variation(CV) of fasting plasma glucose(CV-FPG), large amplitude of glycemic excursions(LAGE). Results Compared with NDF group, the age, diabetic course, serum creatinine, blood uric acid, hyper-sensitivity C reaction protein(hsCRP), Alb/Cr, SDBG, CV-FPG, and LAGE were higher, and total protein, serum albumin, total cholesterol, triglyceride and low density lipoprotein cholesterol were lower in DF group. The difference was statistically significant in hsCRP, SDBG, CV-FPG between the two groups(P＜0.05). Compared with NDF group, the DF with amputation group had significantly increased SDBG, CV-FPG and LAGE(P＜0. 05). Among which, SDBG was also significantly different between DF with amputation and without amputation groups(P＜0.05). Logistic regression analysis showed that hsCRP, Alb/Cr, serum albumin, SDBG and CV-FPG were the independent risk factors for diabetic foot; and that SDBG was the independent risk factor for amputation in DF patients. Conclusion The fluctuations in hsCRP, Alb/Cr, serum albumin, SDBG, CV-FPG are closely related to the development of DF.