Objective: To explore the effect and mechanism of matrine (Mt.) on myocardial interstitial fibrosis induced by pressure overload. Methods: Pressure overloaded myocardial hypertrophy was produced by banding of aorta abdominalis in 67 male Sprague-Dawley rats weighing (200± 15) g. The rats were assigned into one of the following groups: sham-operation control,operation control, operation group treated with matrine (15 mg/(kg.d)) and treated with carvedilol (Car.) (3.6 mg/(kg.d)) group.The rats were given drugs one day after operation. Five weeks after treatment, the left ventricular weight (LVW) was measured and the volume of myocardial cells was detected with Hematoxylin-Eosin (H-E) stain and Masson stain was used to assess the level of fibrosis of the myocardial matrix. Myocardial metalloproteinase activity was quantified with zymography, and survival rate was calculated. Results: Survival rate significantly decreased (P＜0.05), LVW/BW (body weight), MMP-2 (matrix metalloproteinase-2)activity (P＜0.05), size of cardiomyocytes and interstitial fibrosis obviously increased in the operation group compared with sham control group. Mt. and Car. treatment can significantly increase survival rate (P＜0.05), decrease LVW/BW (P＜0.05) and MMP-2 activity (P＜0.05), decrease size of cardiomyocytes and interstitial fibrosis compared with operation group. But there was difference compared with sham group. Conclusion: Matrine was shown to be able to prevent cardiac remodelling of hypertrophy cardium induced by pressure overload including myocardial hypertrophy and fibrosis which may be associated with the decrease in MMP-2 activity of heart.