Objective To observe the intervention effect of asiaticoside ( ASI) on diabetic cardiomyopathy (DCM) mice and to investigate the mechanism. Methods Totally 60 male C57 /BL mice were randomly divided into four groups : Sham group, DCM group, ASI + DCM group, and ASI + DAPT + DCM group. The mice in the Sham group were fed with normal diet and the mice in the other groups were fed with high-fat diet. DCM models were established by injection of streptozotocin combined with high-fat diet. ASI (10 mg/kg• d) was given in the ASI +DCM group. ASI ( 10 mg/kg • d) and DAPT (10 mg/kg • d) were given in the ASI + DAPT +DCM group. The mice in the DCM group were given the same volume of physiological saline. The total time of the experiment was five months. The cardiac function indexes such as left ventricular ejection fraction ( LVEF), left ventricular fractional shortening (FS), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular anterior wall diameter (LVA W d) were detected by ultrasound. The levels of serum creatine kinase isoenzyme (CK-MB) and connective tissue growth factor (CTGF) were detected. The myocardial structure and fibrosis in each group were detected by HE staining and Masson staining. The myocardial apoptosis was detected by TUNEL staining. The mRNA expression levels of Bax and Caspase-3 in the myocardial tissues were detected by RT-PCR. The protein expression levels of Notch1, Hes1, Bax, and Caspase-3 were detected by Western blotting. Results Compared with the DCM group and the ASI + DAPT + DCM group, the muscle fibers in the ASI + DCM group were arranged neatly and the degree of fibrosis was improved. LVEF, FS, L VEDV and Bcl-2, Notch1, Hes1 protein expression levels in the myocardial tissues were lower in the DCM group than in the Sham group, while LVAWd, serum CKMB, CTGF level and Bax, Caspase-3 mRNA and protein expression levels in the myocardial tissues were higher than those of the Sham group (all P < 0. 05). LVEF, FS, and L VEDV in the ASI + DCM group were higher than those in the DCM group, and L VA W d was lower than that of the DCM group ( all P < 0. 05 ) ; LVEF in the ASI + DAPT + DCM group was lower than that of the ASI + DCM group, hut L VEDV was higher ( both P < 0. 05 ) . The levels of serum CK-MB and CTGF and the mRNA and protein expression levels of Bax and Caspase-3 in the myocardial tissues were lower in the ASI + DCM group than in the DCM group and ASI + DAPT + DCM group, while the protein expression levels of Bcl-2, Notch1 and Hes1 in the myocardial tissues were higher than those of the DCM group and ASI + DAPT + DCM group (all P < 0. 05). The apoptosis rates of the DCM group, ASI + DCM group, ASI + DAPT + DCM group were higher than that of the Sham group, and the apoptosis rate of ASI +DCM group was lower than those of the DCM group and ASI + DAPT +DCM group ( all P < 0. 05) . Conclusion ASI can attenuate myocardial injury and reduce myocardial fibrosis in DCM mice, which may be related to the inhibition of Notch1/Hes1 signaling pathway and reduction of cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]