Changes in the estrogen/testosterone balance at menopause may negatively influence the development of diabetic kidney disease. Furthermore, recent studies suggest that changes in hormone levels during perimenopause may influence disease development. Injection of 4-vinylcyclohexene diepoxide (VCD) in B₆C₃F₁ mice induces gradual ovarian failure, preserving both the perimenopausal (peri-ovarian failure) and menopausal (post-ovarian failure) periods. To address the impact of the transition into menopause on the development of diabetes and diabetic kidney damage, we used STZ-induced diabetes in the VCD model of menopause. After six weeks of STZ-induced diabetes, blood glucose was significantly increased in post-ovarian failure (post-OF) diabetic mice compared to cycling diabetic mice. In peri-ovarian failure (peri-OF) diabetic mice blood glucose levels trended higher but were not significantly different from cycling diabetic mice, suggesting a continuum of worsening blood glucose across the menopausal transition. Cell proliferation, an early marker of damage in the kidney, was increased in post-OF diabetic mice compared to cycling diabetic mice, as measured by PCNA immunohistochemistry. In post-OF diabetic mice mRNA abundance of early growth response-1 (Egr-1), collagen-41 and matrix metalloproteinase-9 were increased and 3-hydroxysteroid dehydrogenase 4 (3-HSD4) and transforming growth factor-₂ (TGF₂) were decreased compared to cycling diabetic mice. In peri-OF diabetic mice mRNA abundance of Egr-1 and 3-HSD4 were increased, and TGF₂ was decreased compared to cycling diabetic mice. This study highlights the importance and utility of the VCD model of menopause, as it provides a physiologically relevant system for determining the impact of the menopausal transition on diabetes and diabetic kidney damage.