Objective To investigate the effects of simvastatin(Sim) and losartan(Los) on cardiac fibrosis and myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overloaded rat hearts. Methods The pressure overload model was induced by descending aortic constriction (DAC) in rats. SD rats were randomized into 6 groups (n=20 each) : normol control group, control sham group, DAC group, Los group (DAC+Los, 5 mg/kg), Sire group ( DAC + Sire, 2 mg/kg), Los + Sire group (DAC+Los+Sire, Los 5 mg/kg, Sire 2 mg/kg). Water, Los or Sire drug was administrated by garage daily beginning from day 5 after operation for 30 days. Collagen was measured on Masson stained myocardial sections, and the level of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in left ventricle were detected by RT-PCR. Results Collagen volume fraction (CVF) in DAC group was significantly higher than the normal control and sham groups (P<0.01) which could be significantly reduced by Los and Sire (P<0.05), especially in DAC + Los + Sire group (P<0.01). The levels of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA were also significantly higher in DAC group than in normal control and sham groups (P<0.01). Treatment Sim and Los alone and especially in combination significantly decreased the TIMP-1 mRNA, TIMP-2 mRNA expressions (P<0.01) while MMP-2 mRNA, MMP-9 mRNA levels remained unchanged (P>0.05). Conclusion Upregulation of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA expressions might contribute to myocardial fibrosis in this model, Sire and Los significantly inhibited myocardial fibrosis possibly by downregulating myocardial TIMP-1 mRNA, TIMP-2 mRNA expressions in this model.