Aim To discuss the effect and mechanism of diallyl trisulfide on coronary microembolization (CME) in rats based on the TLR4/MyD88/NF-κB signaling pathway. Methods Sixty SD rats were randomly divided into blank control group, model group, positive control group, low, medium and high dose groups of diallyl trisulfide, 10 rats in each group. The blank control group and model group were given the same volume of normal saline, the positive control group was given rosuvastatin (3.0 mg/(kg·d)), and the diallyl trisulfide low, medium and high dose groups were given diallyl trisulfide (0,0, 40 mg/(kg·d)). After 14 days of pretreatment, CME models were established in the model group, the positive control group, the diallyl trisulfide low, middle and high dose groups by injecting 42 μm microembolic balls into the left ventricle, and the blank control group was injected the same volume of normal saline into the left ventricle. The changes of cardiac function were detected, the area of myocardial microinfarction was detected by HBFP staining, the apoptosis of myocardial cells was detected by TUNEL, the content of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by ELISA, electrochemical method was used to detect troponin I (cTnI) and creatine kinase isoenzyme (CK-MB), the mRNA expressions of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB p65 (NF-κB p65) were detected by RT-PCR, Western blot was used to detect the protein expression of TLR4, MyD88 and NF-κB p65 in rat myocardium. Results Diallyl trisulfide can significantly improve the cardiac function of CME rats, significantly reduce the area of myocardial microinfarction and the apoptotic rate of myocardial cells, effectively inhibit the expression of inflammatory factors IL-1β, TNF-α and myocardial injury indicators cTnI, CK-MB, and significantly reduce the relative expression of TLR4, MyD88 and NF-κB p65 mRNA and protein. Conclusion Diallyl trisulfide can inhibit cardiac dysfunction and myocardial injury in CME rats, and its mechanism may be closely related to TLR4/MyD88/NF-κB signaling pathway.