Background Although diabetic and atherosclerotic vascular diseases have different pathophysiological mechanisms, the screening methods currently used for diabetic lower‐extremity vascular diseases are mainly based on the evaluation methods used for atherosclerotic vascular diseases. Thus, assessment of microvascular perfusion is of great importance in early detection of lower‐extremity ischemia in diabetes. Purpose This cross‐sectional study aimed to develop a quantitative model for evaluating lower‐extremity perfusion. Methods We recruited 57 participants (14 healthy participants and 43 diabetes patients, of which 16 had lower‐extremity arterial disease LEAD). All participants underwent technetium‐99 m sestamibi (99mTc‐MIBI) scintigraphy and ankle‐brachial index (ABI) examination. We derived two key perfusion kinetics indices named activity perfusion index (API) and basal perfusion index (BPI). This study was registered in ClinicalTrials.gov (URL: https://www.ClinicalTrials.gov, NCT02752100). Results The estimated limb perfusion values in our lower‐extremity perfusion assessment (LEPA) model showed excellent consistency with the actual measured data. Diabetes patients showed reduced lower‐extremity perfusion in comparison with the control group (BPI: 106.21 ± 11.99 vs. 141.56 ± 17.38, p < 0.05; API: 12.34 ± 3.27 vs. 14.56 ± 3.12, p < 0.05). Using our model, the reductions in lower‐extremity perfusion could be detected early in approximately 96.30% of diabetes patients. Patients with LEAD showed more severe reductions in lower‐extremity perfusion than diabetes patients without LEAD (BPI: 47.85 ± 20.30 vs. 106.21 ± 11.99, p < 0.05; API: 7.06 ± 1.70 vs. 12.34 ± 3.27, p < 0.05). Discriminant analysis using API and BPI could successfully screen all diabetes patients with LEAD with a sensitivity of 100% and specificity of 80.77%. Conclusions We established a LEPA model that could successfully assess lower‐extremity microvascular perfusion in diabetes patients. This model has important application value for the recognition of early‐stage LEAD in patients with diabetes.