Objective To analyze the effects of different lower extremity arterial disease and tissue microcirculation on negative pressure therapy for diabetic foot ulcer, and to explore the peripheral vascular and tissue microcirculation conditions suitable for the treatment of diabetic foot ulcer with negative pressure wound therapy. Methods A total of 75 patients with diabetic foot ulcer (Wagner grade 2 to 3) who were hospitalized in the Diabetic Foot Treatment Center of Endocrinology and Metabolism Department of Guangxi Zhuang Autonomous Region People's Hospital from November 2015 to November 2019 were selected. According to the results of lower extremity vascular ultrasound, ankle-brachial index (ABI) and percutaneous oxygen partial pressure (TcPO2), the patients were divided into three groups (Group A, Group B and Group C) based on the condition of lower extremity arterial lesions and tissue microcirculation. Each group underwent negative pressure therapy for 2 weeks. Image J graphic analysis software was used to measure the ulcer area and granulation area. Wilcoxon rank sum test and Kruskal-Wallis test were used for comparison between groups. Spearman correlation analysis and multiple linear regression analysis were used to study the correlation and influencing factors of ulcer area reduction value and granulation area increase value at the end of 2 weeks negative pressure therapy. Results The decrease of ulcer area, and the increase of granulation area in three groups (27, 29 and 19 cases respectively) with different lower extremity arterial lesions and tissue microcirculation at the end of 2 weeks treatment were significantly different compared with those before treatment (P<0.05). In the comparison between the three groups, there were statistically significant differences between Group C and Group A, Group B in the value and rate of ulcer area reduction over the end of 2 weeks negative pressure therapy (P<0.05).However, there was no statistical difference between Group A and Group B (P>0.05). Besides, in the comparison between the three groups, there were statistically significant differences between Group C and Group A, Group B in the value and rate of increased granulation area over the end of 2 weeks negative pressure therapy (P<0.05), but there was no statistical difference between Group A and Group B (P>0.05). In addition, the change value of ulcer area at the end of treatment for 2 weeks was correlated with the diabetic duration (r=-0.311), ABI (r=0.394), TcPO2 (r=0.301) and lower limb vascular ultrasound (r=-0.292, P<0.05). The change value of granulation area at the end of treatment for 2 weeks was correlated with TcPO2 (r=0.239, P<0.05) and lower limb vascular ultrasound (r=-0.207, P<0.05).The independent influencing factors of ulcer area reduction at the end of 2 weeks negative pressure therapy were ABI and diabetic course (P< 0.05); the independent influencing factor of granulation area increment at the end of 2 weeks negative pressure therapy was TcPO2 (P<0.05). Conclusions The degree of diabetic lower extremity arterial disease and tissue microcirculation play a role in the efficacy of negative pressure assisted closure technique in the treatment of diabetic foot ulcer. The more severe the lower extremity vascular disease and tissue microcirculation disorder are, the worse the effects of negative pressure wound therapy on ulcer area reduction and granulation growth are. [ABSTRACT FROM AUTHOR]