This article provides a detailed review of the multiple roles of hypoxia-inducible factor-1α in the pathogenesis of diabetic kidney disease, including: regulating angiogenesis, increasing the expression of erythropoietin, modulating oxidative stress through the PI3K/AKT and HIF-1α/HO-1 pathways, promoting inflammatory cell infiltration and the release of inflammatory factors to induce inflammatory responses, facilitating epithelial-mesenchymal transition, pathological angiogenesis, and promoting the release of fibrotic factors, ultimately leading to renal fibrosis. The gene discussed is HMOX1; the disease is renal fibrosis.