Chronic tubulointerstitial nephritis (TIN), characterized by tubular atrophy, interstitial fibrosis and inflammation, is a major prognostic determinant of chronic kidney disease, regardless of the original cause of the kidney disease. Understanding the pathogenesis of TIN has been hampered by the lack of an adequate experimental model. However, the demonstration that the renal lesions of obstructive uropathy induced by experimental urinary obstruction (UO) has provided an excellent model to study the pathogenesis of TIN in general and especially congenital obstructive nephropathy, the most common cause of pediatric end-stage renal disease. Since relief of experimental UO is technically possible, this model is particularly useful for studying the potential reversibility of TIN. Experimental UO is usually created by the unilateral ligation of a ureter. This induces progressive tubular epithelial cell injury, including apoptosis, proliferation, loss of differentiation and atrophy; interstitial inflammatory cell infiltrates composed predominantly of macrophages and T cells; and interstitial fibrosis characterized by an increase and activation of interstitial fibroblasts, deposition of extracellular matrix proteins and loss of peritubular capillaries. These changes collectively lead to progressive scarring and the loss of renal parenchyma and kidney function. The glomeruli and large blood vessels remain either normal or show mild changes later in the course of the disease. In addition to TIN, congenital obstructive nephropathy causes marked derangement of renal and glomerular development. Relief of UO does not seem to reverse TIN. In fact, the renal lesions of obstructive uropathy not only persist, but also progress long after UO is relieved in both adult and neonatal rats. The pathogenesis of UO-induced TIN has been well studied, at least in part because of the ready application of this model to mice, in which genetic manipulation including gene deletion or transfection of putative pathogenic molecules is technically feasible. Experimental UO immediately induces mechanical stretching of tubular epithelial cells and activates the renin-angiotensin system, leading to profound changes of the cells, including neo-expression of a large number of molecules which control cell cycle (e.g. caspases, intrinsic and extrinsic death pathway molecules, inhibitors of cyclin-dependent kinases p27 and p21, reactive oxygen species, and catalase), hypoxic response (HIF- α), epithelial-mesenchymal transformation (e.g. hepatocyte growth factor, bone morphogenic protein 7 and nestin), and the upregulation of cytokines and growth factors (e.g. TGFβ-1, EGF, PDGF, VEGF and TNF-α) as well as chemokines (MCP-1, osteopontin, IL-1, ICAM-1, VCAM-1 and selectins). Inflammatory cells are recruited immediately after UO, probably under the effect of the renin-angiotensin system and later by tubular cell-derived chemokines. Several chemokines and their receptors are also expressed by the infiltrating inflammatory cells, thereby augmenting the recruitment of additional inflammatory cells through an autocrine loop. These molecules are probably also responsible for an increased number interstitial fibroblasts, which are derived not only from the proliferation of resident interstitial fibroblasts, but also from the renal homing of bone marrow-derived fibrocytes and the transformation of tubular epithelial cells, endothelial cells and pericytes into interstitial fibroblasts. Activated interstitial fibroblasts are responsible for the increased synthesis of extracellular matrix protein. This together with an impairment of various fibrolytic pathways leads to the increased deposition of extracellular matrix protein. In summary, typical features of TIN are regularly induced in the experimental model of obstructive uropathy. This versatile model has contributed much to elucidate the mechanism of TIN. The translation of this body of knowledge into TIN in general and its effective treatment of obstructive uropathy remains to be explored.