Objective: The present study aims to use structural equation modeling with multiple regression pathways to examine direct and indirect association of potential behavioral (diet, physical activity and sleep) and cardio-metabolic risk factors with micro-vascular endothelial dysfunction (ED) among middle-aged Chinese males.Methods: The study was conducted in 306 middle-aged Chinese males, who underwent a health checkup between 2018 and 2019. Data on life-style behavior factors (physical activity, diet pattern, sleep quality, and diet data underwent exploratory and confirmatory factor analysis [EFA and CFA] in advance) and cardio-metabolic risk factors referring to metabolic syndrome [blood pressure, triglyceride (TG), fasting blood glucose, high-density lipoprotein cholesterol and body mass index] were introduced into the structural equation model to examine interrelationship among these factors and their association with ED, as evaluated by the reactive hyperemia index (RHI). Results: Impaired ED defined by RHI <1.67 occurred in 39.2% of the participants. Both EFA and CFA identified two major dietary patterns: "prudent pattern" and "western pattern". The univariate test suggested that only TG and prudent dietary pattern were directly associated with RHI. Furthermore, prudent dietary pattern had a direct association with RHI (β=0.16, P<0.05) and an indirect association via triglyceride (Prudent diet→TG: β=-0.15, P<0.05; TG→RHI: β=-0.17, P<0.001). As to confirming the hypothesized association between variables apart, physical activity frequency was correlated to the decrease in TG (β=-0.29, P<0.001), but had no direct correlation to RHI.Conclusion: The network of direct and indirect associations among life-style behavioral and cardio-metabolic risk factors with RHI measured ED among middle-aged males. The most significant modifiable factors identified were TG and prudent diet pattern, which needs to be targeted as preventive strategies for early micro-vascular impairment.