Urine is intrinsically linked to the urinary system, making the urine proteome a valuable resource for investigating renal diseases. Given that urine encompasses a multitude of alterations, accurately determining the underlying causes of changes in the urine proteome poses a significant challenge and holds critical importance for biomarker discovery. To minimize confounding variables, some investigations employed animal models that mimic human pathologies. This chapter underscores the significance of animal models and presents two studies that focused on the serial alterations in urine proteome in animal models of focal segmental glomerulosclerosis and tubular injury diseases. In these experiments, urine samples were collected at various stages of the animal models, with urinary proteins analyzed using LC-MS/MS. In the focal segmental glomerulosclerosis model, 25 urinary proteins exhibited changes throughout the entire process. In the unilateral ureteral obstruction model, 7 and 19 proteins showed significant variation in the 1-week and 3-week groups, respectively. We propose that these stage-dependent dynamic changes in urine proteome within animal models will reinforce the role of urine as a pivotal source for biomarker discovery, particularly concerning kidney diseases, and aid in identifying relevant biomarkers for clinical validation.