AIM: To observe the expression of transforming growth factor ? 1 (TGF-? 1), MAPK 1/3 and fibronectin (FN) in the development of renal tubulointerstitial disease. METHODS: Wistar male rats were randomly divided into normal control group, diabetic group of 1week, 2 weeks, 4 weeks and 8 weeks. Diabetic model was induced by peritoneal injection of streptozotocin. Immunohistochemistry was employed to detect the expression of TGF-? 1, MAPK 1/3 and FN in the kidney. TGF-? 1 protein in the renal cortex was checked by Western blot. BG, Scr and UP were analysed by biochemical methods, and the morphological changes in renal tubulointerstitium were also examined under microscopy on sections stained with HE and PAS. RESULTS: The expression of MAPK 1/3 and FN was observed, but not the expression of TGF-? 1 in normal renal tissue. Positive staining of TGF-? 1 was observed in the renal tubulo-interstitium in 1-week diabetic group and thereafter it increased in the course of diabetes. A continuous increase in the expression of MAPK 1/3 and FN was also observed in two - week diabetic rats. Chronologically the expression of TGF-? 1,MAPK 1/3 and FN and the ratio of KW/BW were positively correlative with each other in diabetic animals except one -week diabetic rats. There was also a positive correlation between MAPK 1/3 and FN in l -week diabetic rats. CONCLUSION: Our data suggest that TGF-? 1 appears in the renal tubulointerstitium in early period of diabetes and then its signal is mediated by MAPK 1/3 cascades to accelerate production of FN ,and in turn leads to renal hypertrophy and tubulointerstitial fibrosis. [