: To determine the association of monocyte-to-high-density lipoprotein ratio (MHR) and neutrophil-to-lymphocyte ratio (NLR) with diabetic macular edema (DME) and early anti-VEGF treatment response. : This was a retrospective and cross-sectional study conducted with 143 patients with diabetes mellitus (53 diabetic retinopathy with DME, 38 diabetic retinopathy without DME, and 52 without diabetic retinopathy). : 13.9 was the best cutoff value to predict DME for MHR, and 2 was for NLR (59% and 75% sensitivity and 81% and 59% specificity, respectively). Logistic regression analysis showed that NLR≥2 and MHR≥13.9 were significantly associated with DME prediction. However, neither NLR≥2 nor MHR≥13.9 was associated with central retinal thickness(CRT) or best corrected visual acuity(BCVA) outcomes after anti-VEGF treatment. On the other hand, increased NLR was associated with inferior CRT outcomes. : MHR and NLR were simple and cost-effective biomarkers to predict DME. Moreover, higher NLR may contribute to poor CRT outcomes.