Abstract: Objective To observe dynamically osteopontin(OPN) expression in the renal tubules of streptozotocin(STZ) induced diabetic rats, and to explore the relationship between OPN and angiotensinⅡ(AngⅡ), nuclear transcription factor-κB(NF-κB), and renal injuries. Methods Male SD rats were injected with STZ to induce diabetes mellitus, which were divided into 5 groups randomly and meanwhile there were other 5 age-matched normal control groups. Immunohistochemistry was employed to observe the expression of OPN, AngⅡ, NF-κB and fibronectin(FN) in renal tubules . The OPN and I-κB protein in renal cortex was detected by Western blot methods. Blood glucose, serum creatinine and 24 h urine protein were examined by biochemistry methods. The renal morphology was checked through light microscopy. Results The AngⅡand NF-κB expression from DM day 3, OPN expression from day7, FN from week 2 in renal cortex or tubules were increased compared with control groups, while I-κB protein in renal cortex was gradually decreased since day 3. In DM week 4, there were positive correlations between OPN and AngⅡ, NF-κB, FN and 24h urine protein. Conclusions Our results suggest that an increase of OPN expression in the renal tubules of diabetic rats may be regulated by AngⅡ and NF-κB, and therefore participates the injury mechanisms of renal tubulo-intestitium.