Objectives This study is designed to investigate the effects and mechanisms of sinomenine (Sin) in stress load-induced heart failure in mice. Methods We used aortic constriction (AB) to cause pressure overload as our heart failure model. Sin was received in mice as the treatment group. Cardiac function and structural changes were detected using echocardiography. Heart–lung mass ratios were measured. The serum levels of IL-10 and IL-17 proteins were detected by using ELISA, cardiac hypertrophy markers atrial natriuretic peptide (ANP), myocardial I and III collagen mRNA levels were detected by RT-PCR. Myocardial type I and III collagen protein levels were detected by Western blotting. Key findings Sin significantly improved stress load-induced heart failure (P < 0.05), reduced the heart–lung mass ratio, ANP, collagen-I and -III mRNA and protein levels (P < 0.05); Sin can enhance the ratio of IL-10/IL-17. Conclusion Sin may be a promising drug target to improve heart failure. Its role is related to reduce serum ANP levels, inhibit the mRNA and protein level of type I and III collagen and enhance the ratio of IL-10/IL-17.