Objective    To study the toxic effects on rat kidney after long-term depleted uranium (DU) exposure.     Methods    Twenty rats of 40 Wistar male rats (35-55 g) were fed with water and feedstuff containing 50 μg/L or 70 μg/kg DU respectively as ingesting group

and another 20 rats served as control. The morphological changes of kidneys were observed by electron microscopy and microscopy after 3-

6-

12-

18- month exposure.  Fibrosis-correlated cytokines such as transforming growth factor beta 1 (TGF-β1)

Smad

tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinases-9 (MMP-9) were analyzed by immunofluorescence and Western blotting. Kidney function and collagen staining were also detected.     Results    At different time points

DU exposure caused pathological changes of the kidneys including glomerulus pyknosis

tubule atrophy and regional renal interstitial fibrosis. The fibrosis aggravated with longer exposure. These cytokines and collagen distribution primarily located on periphery of nephric tubule

and seldom on glomerulus. TGF- 1

Smad

TIMP-1 and MMP-9 in kidneys all increased after DU exposure.     Conclusion    After long-term DU exposure

the rat kidneys showed morphological and ultrastructural changes at different levels. TGF-β1

Smad

TIMP-1 and MMP-9 all take part in the process of kidney fibrosis.