Abstract Background and Aims Chronic inflammation and renin-angiotensin system (RAS) overactivation have been demonstrated as a central mechanism that results in the development of progressive chronic kidney disease (CKD). Evidences have indicated that tertiary lymphoid tissues (TLT) form after acute kidney injury (AKI), especially in old-aged mice. Heterogeneous fibroblasts which appear and secret proinflammatory cytokines after AKI underlie TLT formation. There is an association between TLT sizes and impaired renal function along with increase of proinflammatory cytokines, suggesting a probable cause of persistent inflammation after AKI. In this study, we explored the relationship between TLT development and RAS activity. The phenotypes of heterogeneous fibroblasts diversified after AKI is also investigated. Method Here we utilized ischemia-reperfusion injury to cause ensuing CKD both in a CD-1 and C57BL6J mice model. We also used staining of CD3 and B220 to label and confirm multiple TLTs which represents T and B lymphocytes respectively. Results Administration of losartan, a kind of RAS inhibitor, offered protection against subsequent CKD development and attenuated number and size of TLT besides blood pressure reduction. Moreover, heterogeneous fibroblasts diminished and proinflammatory cytokines such as CXCL13, CCL21 and CCL19 which trigger the initiation of TLT were downregulated. In experiments of several fibroblast cell lines, angiotensin II (Ang II) administration could induce differentiation of fibroblasts with distinct phenotypes expressing p75 neurotrophin receptor and retinaldehyde dehydrogenase 2 which contribute to TLT formation. These fibroblasts expressing PDGFRβ stimulated production of aforementioned proinflammatory cytokines and expression of pro-fibrotic genes. Conclusion Our data demonstrates that TLT plays an important role in AKI-CKD transition. We also verify that Ang II causes phenotypic change of fibroblasts which constitute TLT. Losartan can ameliorate TLT formation through inhibition of these distinctive fibroblasts. It is a plausible mechanism to reduce ensuing CKD.