Objective:To observe the cardioprotective effect of Kuoxinfang on tnnt2a mutant zebrafish model with similar phenotype to dilated cardiomyopathy and explore the possible mechanism of action. MethodsThe normal wild-type zebrafish were used in the control group, the tnnt2a mutant zebrafish were used in the model group and the tnnt2a mutant zebrafish that received Kuoxinfang 5 μg/ml were used in the Kuoxinfang group. The effect of Kuoxinfang on tnnt2a mutant zebrafish was studied and the survival rate, sinus venosus-bulbus arteriosus (SV-BA) distance, HE staining of pathological sections, ATP content and expression of the apoptosis-related gene bcl-2/bax were observed.  Results:Compared to the model group, Kuoxinfang has protective effect on the heart of tnnt2a mutant zebrafish, as it improves the survival rate, increases the ATP content and upregulates expression of the bcl-2/bax gene in zebrafish of the model group (P<0.05, P<0.01).  Conclusion:Kuoxinfang shows cardioprotective effect in the tnnt2a mutant zebrafish model, and the mechanism may be associated with improvement in energy metabolism and reduction in apoptosis of cardiomyocytes.