Aim To observe the effect of cardiac glucocorticoid receptor activation on cardiac remodeling and cardiac function after myocardial infarction (MI) in mice and its possible mechanism. Methods 28 male C57BL/6J mice were randomly divided into sham group, dexamethasone group, MI group and MI＋dexamethasone group, 7 mice in each group. The MI group ligated the left anterior descending coronary artery in mice to create an MI model; the sham group and the dexamethasone group only wound the thread without ligation, and injected normal saline or dexamethasone (20 mg/kg) by intraperitoneal injection 24 h before the operation; the MI＋dexamethasone group was injected with dexamethasone (20 mg/kg) by intraperitoneal injection 24 h before creating MI model. On the 7th day after surgery, small animal ultrasound was used to detect cardiac function indicators, heart tissue slices were taken and immunohistochemical staining was used to observe the activation level of glucocorticoid receptors, Masson staining was used to observe the infarct area, immunohistochemical staining was used to observe the levels of inflammatory factor IL-6 and chemokine CCL-5. Results Compared with the MI group, in the MI+dexamethasone group the left ventricular end-diastolic diameter reduced by 6.85%, the left ventricular end-systolic diameter reduced by 6.89%, the left ventricular end-diastolic volume reduced by 16.11%, the left ventricular end-systolic volume reduced by 17.18% (all P＜0.05), the ejection fraction increased by 10.63%, and the fractional shortening rate increased by 13.11% (all P＜0.05), indicating that dexamethasone pretreatment improved cardiac function in mice after MI; the level of phosphorylated glucocorticoid receptor increased 1.57 times; after MI, the infarct area decreased by 18.4% (P＜0.05); the expression level of inflammatory factor IL-6 decreased by 71.4%, and the expression level of chemokine CCL-5 decreased by 65% (all P＜0.05). Conclusion Activation of cardiac glucocorticoid receptors has an antagonistic effect on myocardial cell damage in mice after MI, which can improve myocardial remodeling, this effect may be related to its anti-inflammatory response.