CDA1 is a nuclear protein which has been identified to be an enhancer of the TGF-β signalling pathway. This action of CDA1 is critical in the progression of fibrosis, as demonstrated in mouse models of diabetes-associated atherosclerosis and nephropathy. Importantly, elevated expression levels of CDA1 were observed in diabetic and non-diabetic renal fibrosis in man. The antifibrotic efficacy of targeting CDA1 in renal fibrosis was recently demonstrated in vivo using global CDA1 knockout mice. Whether an induced genetic knockout of CDA1 before or during the progression of disease will be able to prevent or attenuate the development of fibrosis has yet to be experimentally investigated. Thus, the aim of this study was to examine the effect of an induced genetic deletion of CDA1 on the progression of renal fibrosis in a streptozotocin-induced mouse model of diabetic nephropathy. Male CDA1flox/ERCre mice were rendered diabetic with streptozotocin or injected with buffer alone to serve as non-diabetic controls. These mice were administered with tamoxifen to delete the CDA1 gene after 5 weeks of diabetes, or injected with corn oil to serve as CDA1 “wildtype” controls. CDA1flox mouse strain ran parallel to serve as a genotype control. Mice were culled and tissues collected for analysis after 10 weeks of diabetes. Diabetic mice exhibited changes in metabolic parameters such as increases in plasma glucose and glycated haemoglobin, as well as polyuria, polydipsia and renal hypertrophy, as expected. Tamoxifen administration or the presence of ERCre had no effect on any of these parameters. Renal CDA1 mRNA expression was reduced by ~70-80% (p<0.05) in CDA1flox/ERCre mice administered with tamoxifen, regardless of diabetic status. Expression levels of profibrotic genes, such as fibronectin, CTGF and collagen I, were elevated by ~2-, ~1.6- and ~1.5-fold, respectively (p<0.05) in diabetic CDA1flox/ERCre mice with corn oil. This increase was attenuated by ~40-70% (p<0.05) in diabetic CDA1flox/ERCre mice with tamoxifen, where CDA1 gene was deleted at 5 weeks of diabetes. In conclusion, reduction in CDA1 expression at 5 weeks of diabetes was able to attenuate diabetes-associated increases of profibrotic gene expression, whilst having no effect on metabolic parameters.