Abstract: Objective To investigate the role of NLRP3 inflammasome in type 2 diabetes mellitus with diabetic foot. Methods From June, 2016 to June, 2017, 100 patients with type 2 diabetes mellitus and diabetic foot treated in our hospital were selected as an observation group, and 50 patients with type 2 diabetes mellitus (without diabetic foot) were selected as a control group. The expression of NLRP3 between the two groups were observed. In addition, the main clinical features of the patients in the observation group were collected, and the correlation between the NLRP3 inflammasome and the clinical features of diabetic foot were analyzed. Results When compared with the control group, the relative expression of mRNA of the NLRP3 inflammasome increased significantly in the observation group(4.12±0.88 vs. 2.73±0.92, P<0.001), and the relative expression level of NLRP3 inflammasome protein increased significantly(12.48±2.81 vs. 9.89±2.65, P<0.001). The NLRP3 inflammasome mRNA expression in patients of 0-1, 2-3 and 4-5 Diabetes severity grading were 3.27±0.78, 3.87±0.83 and 4.83±0.92, the difference was statistically significant (P=0.002). NLRP3 inflammasome protein expression levels were 9.65±2.12, 11.32±2.54 and 15.49±2.98, the difference was statistically significant (P<0.001). Pearson linear correlation analysis showed that the relative expression level of NLRP3 mRNA and the relative expression of NLRP3 inflammasome protein were all directly proportional to the diabetic foot severity score and glycosylated hemoglobin (P<0.05). Conclusion The activation of NLRP3 inflammasome in patients with type 2 diabetes mellitus combined with diabetic foot is related to the development of diabetic foot.