The aim of this observational case control study was to evaluate the association of diabetes and diabetic retinopathy (DR) with retinal ganglion cell loss. Cases were Chinese patients with type 2 diabetes with and without DR, aged 40-80 years. Eligible cases were matched to controls, who were volunteers without diabetes, on the basis of age and gender. Retinal scans were performed on cases and controls using Cirrus HD-OCT. The ganglion cell analysis algorithm, incorporated into Cirrus HD-OCT, was used to demarcate and measure the thicknesses of the ganglion cell inner plexiform layer (GC-IPL), retinal nerve fibre layer (RNFL) and the outer retina. Retinal photography was performed to assess diabetic retinopathy severity, using a scale modified from the Airlie house Classification system; 227 cases and 227 controls were included in the analysis. Results showed that all subjects with diabetes (with and without DR) had significantly thinner average GC-IPL and average RNFL, but not average outer retinal layer than controls. Cases with any DR had thinner GC-IPL than controls. Among cases, subjects with moderate or severe DR had thinner GC-IPL than subjects with no DR. The authors conclude that retinal ganglion cell loss is present in subjects with diabetes and no DR, and is progressive in moderate or severe DR.