Abstract: Objective To investigate the changes of the mRNA expressions of membrane type 3-matrix metalloproteinase (MT3-MMP) and tissue inhibitor of matrix metalloproteinase 2 (TIMP2) in diabetic rat kidneys and the effect of losartan on such changes. Methods Three groups of male Wistar rats were used in this study, namely group A as the control group (n=11), group B consisting of diabetic rats without any therapy (n=11), and group C treated with losartan (n=9). Six months after treatment, the kidneys were taken from the rats to measure the mRNA expressions of MT3-MMP, TIMP2 and transforming growth factor β1(TGFβ1)with reverse transcriptional PCR (RT-PCR), and observe the glomerular basement membrane thickening and mesangial matrix(MM)density (MM area/mesangial area) with electron microscope. Twenty-four-hour urine was also collected to measure urinary albumin excretion (UAE). Results The expression of renal MT3-MMP mRNA in group B (1.37±0.96) was significantly stronger than those in group A (0.75±0.34, P<0.05) and in group C (0.75±0.30, P<0.05). The mRNA expression of renal TIMP2 in group B (0.73±0.37) was significantly increased as compared with group A (0.32±0.19, P<0.05) and group C (0.34±0.17, P<0.05), with a higher mRNA expression of renal TGFβ1 in grour B (0.53±0.20 vs 0.26±0.13 in group A and 0.29±0.15 in group C, P<0.05). UAE in group B (2.18±1.98mg) was significantly higher than those in groups A and C (0.41±0.47mg/d, P<0.05; 0.65±0.89 mg/d, P<0.05, respectively). The glomerular basement membrane thickness (532±108 nm) and the MM density (56.4±6.8) were significantly greater in group Bthan in the other two groups (P<0.05). Conclusions MT3-MMP and the TIMP2 mRNA expressions are significantly increased in diabetic rat kidneys. Losartan can prevent the development of diabetic nephropathy and inhibit MT3-MMP and the TIMP2 mRNA expressions in diabetic rat kidneys.