Abstract: OBJECTIVE To observe the effect of leonurine on rats with ventricular remodeling induced by isoproterenol(ISO) and to explore the possible mechanism involved. METHODS SD rats (n=10) were used as normal control group， and 80 rats were given ISO by intraperitoneal injection daily for 2 weeks to establish the model of ventricular remodeling. The model rats were divided into 5 groups randomly as model group， low-dose leonurine (7.5 mg/(kg·d)) group， middle-dose leonurine (15 mg/(kg·d)) group， high-dose leonurine (30 mg/(kg·d)) group and p38MAPK inhibitor (0.3 mg/(kg·d)) group. After the treatment for 2 weeks， the pathological change of left ventricular myocardial tissues was observed by HE staining，and the expression of TGF-β1 was determined by the method of immunohistochemistry. The serum concentrations of ET-1 and NO were measured by ELISA and nitrate reductase methods， respectively. The expression of p38MAPK， MEF2，β-MHC and α-MHC mRNA was detected by qPCR， and the protein expression of ET-1， p-p38MAPK and MEF2 was determined by Western blot. RESULTS Compared with model group， the pathological change of ventricular remodeling in high-dose leonurine group was attenuated， and the serum concentrations of NO and the mRNA expression of α-MHC in left ventricular myocardial tissues of high-dose leonurine group were higher (P<0.05).The expression of TGF-β1， the serum concentrations of ET-1， the mRNA expression of p38MAPK，MEF2 and β-MHC mRNA， and the protein expression of ET-1， p-p38MAPK and MEF2 were lower than those in model group (P<0.05). CONCLUSION Leonurine attenuates ventricular remodeling in the rats induced by ISO， and it is potentially associated with inhibiting p38MAPK/MEF2 signaling pathway.