Abstract: To study the mechanism of curcumin and/or aerobic exercise improving pyroptosis in myocardium of hyperlipidemic rats. Fifty 5-week-old male SD rats were randomly divided into normal diet control group (RDC), high fat diet control group (HDC), high fat diet with curcumin group (HDCC), high fat diet with aerobic exercise group (HDM), high fat diet with curcumin and aerobic exercise group (HDCM), ten in each group. From the third week, group HDCC and HDCM were injected intragastrically with curcumin at 400 g/(kg·d), and the other groups were given an equal volume of 0.5% sodium carboxymethylcellulose. Group HDM and HDCM performed aerobic exercise intervention, and the other groups did not. Twenty-four hours after the end of 6-week-intervention, the myocardial microstructure in each group was observed, blood and myocardium related biochemical indicators were tested. The results showed that, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), HDC were significantly higher than RDC (P<0.01). Serum TC and TG, HDCC, HDM and HDCM were significantly lower than HDC (P<0.01). Serum TC, HDCM decreased significantly compared with HDCC and HDM (P<0.05 or P<0.01). Serum LDL-C, HDCC and HDCM were significantly lower than HDC (P<0.05 or P<0.01), HDCM was significantly lower than HDCC and HDM (P<0.05 or P<0.01). Serum high-density lipoprotein cholesterol (HDL-C), HDC was significantly lower than RDC (P<0.05), HDCC, HDM and HDCM significantly were higher than HDC (P<0.05 or P<0.01), HDCM was significantly higher than HDM (P<0.01). The myocardial microstructure of RDC was normal, there were inflammatory injury in myocardium of HDC, injury in HDCC, HDM, HDCM were improved significantly, and HDCM was the most significant in the three. Myocardial interleukin-1β (IL-1β) and interleukin-18 (IL-18), HDC was significantly higher than RDC (P<0.01), HDCC, HDM and HDCM were significantly lower than HDC group (P<0.01), HDCC and HDM were significantly higher than HDCM (P<0.05 or P<0.01). Myocardial injury marker creatine kinase-MB (CK-MB), HDC was significantly higher than RDC (P<0.01), HDCC, HDM and HDCM were significantly lower than HDC (P<0.01), HDCM was significantly lower than HDCC and HDM (P<0.01). The H-score of myocardial NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and cysteinyl aspartate specific proteinase 1 (Caspase1), HDC was significantly lower than RDC (P<0.01), HDCC, HDM and HDCM were significantly higher than HDC (P<0.05 or P<0.01), HDCC and HDM were significantly lower than HDCM (P<0.05 or P<0.01). Therefore, the 6-week curcumin and/or aerobic exercise intervention could improve pyroptosis in myocardium of hyperlipidemic rats, inhibit excessive inflammatory response, and protect the heart function/structure, which might be related to inhibiting NLRP3/Caspase1 pathway. The effect of combined intervention was better.