Objective To investigate the effect of aspirin on myocardial fibrosis and inflammation in diabetic rats and the molecular mechanism underlying this effect. Methods Male, specific pathogen free-grade SD rats were randomly divided into three groups: the control group (Control group), the diabetes mellitus group (DM group), and the aspirin intervention group (Aspirin group). The DM group received an intraperitoneal injection of streptozotocin (STZ; 60 mg / kg) to induce diabetes; the Control group received an intraperitoneal injection of the same volume of normal saline; and the Aspirin group received an intraperitoneal injection of STZ 60 mg / kg, followed by administration of aspirin (1 mg / kg per d) by oral gavage for 10 weeks. Echocardiography was used to detect changes in cardiac structure and function; Masson’ s trichrome staining was used to observe myocardial fibrosis; ELISA was used to detect myocardial inflammatory factors (IL- β, IL-6, TNF-α); and RT-PCR and Western blot were used to detect CTRP6 expression in myocardial tissue. Results Compared with the Control group, the DM group had abnormal cardiac function and structural damage, significant myocardial fibrosis, and significantly increased myocardial IL-1β, IL-6, and TNF-α levels ( P < 0. 01). RT-PCR and Western blot showed that CTRP6 expression was significantly reduced in myocardial tissues (P <0. 01). Compared with the DM group, the Aspirin group showed greater cardiac function recovery, greater structural improvement, significantly reduced myocardial fibrosis, decreased IL-1β, IL-6, and TNF-α expression in myocardial tissues (P <0. 05, P <0. 01), and increased CTRP6 mRNA and protein expression in myocardial tissues (P <0. 05, P <0. 01). Conclusions Aspirin can inhibit myocardial fibrosis and inflammation in diabetic rats, and the mechanism of this effect involves increased CTRP6 expression.