Purpose: To compare segmented retinal layer thicknesses between male and female diabetics with clinically significant macular edema (CSME). This study expands our earlier analysis of central macular thickness (CMT) measurements in diabetic males vs. females. Methods: Diabetic retinopathy screening of 2080 diabetics from Alameda County, CA, indicated 142 patients with CSME, as judged by EyePACS certified graders using color fundus images (Canon CR6-45NM). Of the 2080 diabetics, 1784 were imaged with SD-OCT (Optovue iVue). From the 142 patients, we selected 11 males with good fixation, CMT > 300 µm, and no other ocular complications, along with 11 females with the greatest values of CMT while controlling for age, HbA1c and diabetes duration. Manual segmentation of retinal layers using custom software (Mathworks Matlab) of the SD-OCT images of these subjects was done. We analyzed thicknesses for regions 1 deg - 2 deg for nasal and temporal retina in a B-scan centered on the fovea. A 2 X 2 ANOVA probed the differences in thickness for gender, meridian, and their interaction. We also analyzed the central 1 mm of the outer retinal layers, and performed t-tests. Results: Males had significantly thicker nerve fiber layer (NFL) (13.30 ± 2.85 µm) than females (10.13 ± 6.13 µm) and ganglion cell layer-inner plexiform layer (GCL-IPL) (62.54 ± 21.18 µm) than females (48.07 ± 25.91 µm), p < 0.05. There was no effect of meridian and no interaction (p > 0.05). All other layers except the retinal pigment epithelium (RPE) were thicker for males than females even though these were not significant (p > 0.05). There were no significant differences for the layers of the outer retina, which were highly variable and distorted by cysts. Conclusion: Outside the fovea, NFL and GCL-IPL thicknesses were significantly higher in males than females.