Role of active DNA methylation-hydroxymethylation in regulation of Rac1 transcription is further confirmed by our results showing increased 5hmC levels at the Rac1 promoter in the retinal microvessels from mice diabetic for 2 weeks, and amelioration of diabetes-induced activation of Rac1 (transcription and activity) by Dnmt1-siRNA. This evidence concerns the gene DNMT1 and diabetes mellitus.