Renal tubular epithelial cells (TECs) play a critical role in driving acute kidney injury (AKI) progression, but the key molecular features in TECs during this process is not clear. To better understand the molecular characteristics in renal TECs during AKI and renal fibrogenesis, an irreversible AKI mouse model induced by ischemia/reperfusion injury (IRI) was used in this study. The renal tubules were isolated and tubule specific transcriptome was detected by RNA-seq at different stages in the progression of AKI in this model. The overall transcriptome indicated injury and repair process of TEC after renal IRI. In addition, metabolism maladaption was observed during AKI progression to chronic fibrosis. Particularly, we found dysregulation of multiple steps of lipid metabolism in tubule transcriptomes. Oil red O staining revealed massive lipid droplets accumulation in TECs at day 10, thus confirming the defect of lipid metabolism. This is the first study to charaterize renal tubule specific transcriptome during AKI progression. The results shed light on the molecular features in TECs for progressive AKI.