Coronary microvascular disease (CMVD) is commonly observed among individuals presenting with chest pain, though its underlying pathological mechanisms remain incompletely elucidated. Emerging evidence suggests that hyperinsulinemia serves as a critical factor in cardiovascular dysfunction development, potentially contributing to CMVD pathogenesis. This investigation aims to examine the potential link between hyperinsulinemia and CMVD manifestation in clinical populations.This study enrolled 347 patients presenting with ischemic chest pain but without obstructive coronary artery disease. All participants underwent coronary flow reserve (CFR) assessment through transthoracic Doppler echocardiography. Patients demonstrating CFR values below 2.0 were classified into the CMVD group (n=105), while those with CFR≥2 constituted the non-CMVD group (n=245). Biochemical parameters including fasting insulin (FINS), fasting blood glucose (FBS), and glycosylated hemoglobin (HbA1c) were quantitatively analyzed. Based on FINS concentration tertiles, participants were stratified into low-insulin (n=118), medium-insulin (n=114), and high-insulin (n=115) subgroups. Multivariate logistic regression analysis was employed to calculate adjusted odds ratios (OR) with corresponding 95% confidence intervals (CI) for CMVD risk assessment.CMVD patients exhibited elevated concentrations of FINS, FBS, HOMA-IR, and HbA1c compared to non-CMVD counterparts. CMVD cases demonstrated greater prevalence of female gender, diabetes mellitus, and hypertension (P 12.4 μIU/mL) as an independent predictor for CMVD (OR 2.279, 95% CI 1.046-4.967). Additional independent risk factors included diabetes (OR 1.920, 95% CI 1.049-3.513), female sex (OR 3.218, 95% CI 1.858-5.572), hypertension (OR 1.746, 95% CI 1.013-3.007), and advancing age (OR 1.036, 95% CI 1.005-1.069) (P < 0.05).Hyperinsulinemia is associated with impaired coronary microvascular function. Hyperinsulinemia serves as a significant independent contributor to the development of CMVD, demonstrating a clear pathological relationship beyond conventional risk factors.