Background Associated factors and microvasculature change of clinically significant macular edema (CSME) were fully studied. This study was intended to investigate the associated factors and macular vascular perfusion change for diabetic macular edema (DME) at the early stage. Methods This study was a cross-sectional observational study. A total of 255 eyes of 128 diabetes mellitus patients were enrolled and underwent a serious of ophthalmological and systemic evaluation. Early DME was characterized by central subfoveal thickness (CST) value between 250µm and 325µm, detectable inner retinal layers, intact ellipsoid zone and external limiting membrane. While non-DME was characterized by CST <250µm with normal retinal morphology and structure. Results Treatment method, age, body mass index, diabetic duration, HbA1c level, total cholesterol, triglycerides, blood urea, blood pressure, proteinuria, serum creatinine and estimated glomerular filtration rate (eGFR) were not associated with early DME development. Male, HbA1c level ≤ 8% and cumulative insulin dosage ≥ 30000U were significantly associated with higher risk of early DME. Vessel density, microaneurysms number and hyperreflective foci number were not significantly different between non-DME and early DME patients. Foveal avascular zone (FAZ) area ≤ 0.3mm2 was significantly associated with higher risk of early DME. Correlation analysis results showed that FAZ area was not correlated with cumulative insulin dosage, age, or diabetes duration. Conclusions Higher cumulative insulin dosage, lower HbA1c level and male could be risk factors for early DME development. Compared to non-DME, early DME showed a significant FAZ area reduction. Our results highlighted the important role of insulin in early DME development, indicated an early worsen of DME with tight blood glucose control and suggested an intervention of insulin-related retinal impairment.