To study correlation of different optical coherence tomography (OCT) patterns of diabetic macular edema (DME) with systemic risk factors. Institutional cross-sectional double-masked non-interventional study with 330 eyes of middle-aged male type 2 diabetes patients with DME. Various systemic parameters were measured. Diffuse retinal thickening (DRT), cystoid and serous patterns of DME were identified on OCT. Comparison between DRT versus non-DRT and serous versus non-serous eyes was done in respect to systemic parameters. Correlation of serous and DRT pattern was tested with systemic parameters above and below specified values. Mean age was 54.4 ± 7.1 years. Mean duration of diabetes was 8.7 ± 4.2 years. Mean serum globulin level was significantly higher (p = 0.018) in serous compared to non-serous group. Prevalence of serous DME was significantly high in those with serum globulin level >3.5 gm/dl (prevalence ratio = 3.01, p = 0.040). Significant correlation of central macular thickness was observed with duration of diabetes (p = 0.002, r = 0.440).Visual acuity (logMAR) was correlated significantly with HbA1C (p = 0.031, r = 0.305). Increased serum globulin, a positive phase reactant of inflammation, was found significant independent risk factor for development of serous DME. This study did not identify any modifiable systemic factor for any of the OCT patterns in DME.