Objective To investigate the application value of two-dimensional shear wave elastography (2D-SWE) in assessing renal fibrosis in mice with hypertensive nephropathy. Methods C57 mice were randomly divided into normal control and model groups. Ten normal control mice were perfused with saline using a microosmotic pump, and the model group was perfused with angiotensin II using a microosmotic pump. The model group was divided into hypertensive nephropathy group I, II, III and IV according to the duration of modeling, with 5 mice in each group. The changes of blood pressure were measured before and after modeling; the renal cortical stiffness of mice at different modeling stages were measured by 2D-SWE technique; the glomerular capillary basement membrane structure was observed by transmission electron microscopy; urea nitrogen (BUN), serum creatinine (Scr) and 24 h urinary protein (24 h UP) were quantified by enzyme-linked immunoassay. The expression of α-smooth muscle actin (α-SMA), collagen type I (collagen-Ⅰ) and collagen type III (collagen-Ⅲ) in renal tissues was detected by Western Blot. collagen-III) expression in kidney tissues. Results The blood pressure of mice increased significantly after the end of modeling; the damage of capillary endothelial cells and segmental wrinkling of basement membrane in kidney tissues were observed by transmission electron microscopy; the 2D-SWE technique in groups III and IV of hypertensive nephropathy showed a significant increase of renal cortical stiffness measurement in mice; HE and Masson staining showed severe tubular damage, even vacuolar degeneration, epithelial cell detachment and inflammatory Western Blot showed that the protein expression levels of α-SMA, collagen-Ⅰ and collagen-Ⅲ were increased. Conclusion The renal cortical stiffness detected by 2D-SWE technique was positively correlated with the degree of renal fibrosis in mice, and 2D-SWE technique is of great clinical application for the assessment of renal fibrosis in hypertensive nephropathy.