Purpose: To evaluate the change in broadband (W/W), red on blue (R/B), and blue on yellow (B/Y) photopic negative response (PhNR) in patients with diabetes mellitus with no diabetic retinopathy (no DR) and different stages of DR and compare it with age-matched controls. This study was performed to provide a single PhNR protocol that can be used for early diagnosis of DR. Methods: It was a cross-sectional case-control study done in a hospital setup. Patients with diabetes with no DR and different stages of DR with no other associated ocular pathologies were included. Age-matched controls with no retinal pathologies were also included for comparison. All subjects underwent detailed ophthalmic examination and W/W, R/B, and B/Y electroretinography. Fifty control eyes and 52 treatment naive eyes of 52 patients with diabetes [no DR = 11, mild nonproliferative diabetic retinopathy (NPDR) =11, moderate NPDR = 10, severe NPDR = 9, and proliferative DR = 11] were included in the study. Results: On comparing the ERG responses in patients with diabetes and age-matched controls, a significant reduction (P < 0.05) was noted in the amplitudes of a-wave (39.78 +/- 11.34 mu V vs. 67.28 +/- 12.88 mu V), b-wave (116.25 +/- 45.25 vs. 134.39 +/- 28.78 mu V), W/W PhNR (33.86 +/- 17.33 vs. 67.18 +/- 15.99 mu V), R/B PhNR (28.77 +/- 15.85 vs. 53.48 +/- 14.15 mu V), and B/Y PhNR (55.04 +/- 32.63 vs. 104.79 +/- 24.37 mu V). Post hoc analysis revealed that all the eyes in the diabetic group, including those with no DR, had a significantly reduced PhNR amplitude (P < 0.05) when compared with controls. PhNR was found to reduce in amplitude with increasing severity of DR (P < 0.05), with more significance in B/Y. Receiver operating characteristic showed highest area under the curve in B/Y PhNR (94%, P < 0.001), with maximum sensitivity and specificity of 88% and 87%, respectively. Conclusion: Changes in the amplitude and implicit time of ERG can reflect the severity of DR. PhNR amplitudes, especially B/Y PhNR, appear to be significantly reduced even in eyes with no DR.