Objective To observe the expression of tissue transglutaminase (tTG) in renal tissues of diabetic nephropathy rats， and to investigate its contribution to the progression of diabetic nephropathy. Methods Streptozotocin-induced diabetic rats were sacrificed at 30 d， 60 d， 90 d， and 120 d respectively. Albuminuria excretion rate (AER)， kidney weight index and serum creatinine (Scr) of the rats were measured. Hematoxylin and eosin (HE) staining and periodic acid-silver-methenamine (PASM) staining were used to observe the renal pathological changes. Collagen Ⅳ(Col Ⅳ) and soluble tTG protein in kidney were examined by immunohistochemistry，insoluble tTG by immunofluorescence. Expression of total tTG mRNA in kidney was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results AER， kidney weight index and Scr of diabetic rats were all progressive during the period of the experiment. Compared with control group， the levels of Col Ⅳ， soluble tTG and insoluble tTG protein in kidneys of hyperglycemic rats were significantly increased at 30 d， 60 d， 90 d and 120 d(P < 0.05，P < 0.01).During the whole course， levels of Col Ⅳ，soluble tTG and insoluble tTG of kidneys from diabetic rats increased gradually.Both soluble tTG expression and insoluble tTG expression were positively correlated with AER( r=0.937，P < 0.01 and 0.809，P < 0.01). The location of increased Col Ⅳ in the glomeruli was the same as that of increased insoluble tTG in the mesangium， and the correlation coefficients of insoluble tTG and Col Ⅳ was 0.831 (P < 0.05). Total tTG mRNA levels started to rise in diabetic kidneys at 30 d， reaching its peak at 90 d， and reduced slightly at 120 d. Conclusion The over-expression of tTG protein and the change of total tTG mRNA levels in the diabetic kidney，and the positive correlation of insoluble tTG and Col Ⅳ in glomeruli demonstrates that tTG may play a role in the progression of early diabetic nephropathy.