Objective To investigate the improving effects of Shenshao decoction on myocardial structure and function in diabetic cardiomyopathy,and its effect on expression of TLR4/MyD88-dependent pathway signal in diabetic cardiomyopathy. Methods Diabetes mellitus was induced in 8-week-old male Wistar rats by a single intraperitoneal injection of streptozotocin. The changes of plasma myocardial enzyme (CK, LDH) and high sensitive C reactive protein (hsCRP) were measured. Cardiac function was measured by left ventricular intubation. Hematoxylin and eosin staining and electron microscopy were used to observe the changes of myocardial morphology and ultrastructure in rats. Expression of Toll-like receptor 4(TLR4), myeloid differentiation protein 88(MyD88), and nuclear factor-κB P65(NF-κB P65) were tested by immunohistochemistry. Results After 6 weeks of treatment, the left ventricular diastolic and systolic functions were obviously improved;the degrees of myocardial fibers and mitochondrial damage were obviously relieved;the content of CK, LDH and hsCRP decreased (P<0.05), and hsCPR was positively correlated with CK and LDH (r=0.823,r=0.819,P<0.05).The expressions of TLR4, MyD88, NF-κB P65 were significantly decreased (P<0.05).There was no significant difference in the above mentioned indicators between the control group and control+Shenshao decoction group (P>0.05). Conclusions Shenshao decoction can reduce the myocardial injury in diabetic cardiomyopathy and improve cardiac diastolic and systolic functions.The mechanism may be related to attenuated inflammation by TLR4/MyD88 dependent signaling pathway.