Diabetic retinopathy (DR) is a major cause of blindness globally. The lack of suitable non-transgenic mouse models of DR has hindered understanding the mechanisms and the development of interventions for DR. In this study, BXD and Collaborative Cross recombinant panels were screened after chemically-induced diabetes to identify a DR mouse model. The BXD strains did not develop DR . Of 61 tested Collaborative Cross strains, 3 strain showed DR features. The FOT stain was the most suitable strain with retinal vascular and neural changes representing hallmark features of DR, and microarray studies showing significant differential expression of several DR genes.