Aim To explore the protective effect and potential mechanism of ursolic acid (UA) on acute myocardial infarction (AMI) in mice. Methods 30 C57 mice were randomly divided into sham group, AMI model group and ursolic acid group. AMI model group and ursolic acid group were ligating left anterior descending artery for 30 min. The myocardial and serum in the three groups were collected after reperfusion for 4 h. NBT and HE were used to evluate the myocardial infarct size and myocardial pathological changes, respectively; automatic biochemical analyzer test was used to detect the expression of creatine phosphokinase (CPK), cardiac troponin I (cTnI), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and high density lipoprotein cholesterol (HDLC) in the serum; thiobarbituric acid (TBA) method was used to examine myocardial malondialdehyde (MDA), lipid peroxide (LPO) and free fatty acid (FFA); enzyme xanthine oxidase method was used to detect the activity of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the heart; the activity of plasma 6-Keto prostaglandin F₁α(6-Keto-PGF₁α) and the content of thromboxane A2 (TXA2) was detected by radiation immunoassay in plasma. Results Compared with sham group, AMI model group had higher myocardial infarct size, more myocardial pathological changes and higher expression of LDH, cTnI, CPK, TC, TG, LDLC, MDA, LPO, TXA2 and the content of FFA in myocardial infarction area and non infarct area with lower activity of CAT, GPx, SOD and the expression of 6-Keto-PGF₁α and HDLC. Compared with AMI model group, ursolic acid group had lower myocardial infarct size, less myocardial pathological changes and lower expression of LDH, cTnI, CPK, TC, TG, LDLC, MDA, LPO, TXA2 and the decreased content of FFA in myocardial infarction area and non infarct area with higher activity of CAT, GPx, SOD and expression of 6-Keto-PGF₁α and HDLC. Conclusion Ursolic acid had an obvious protective effect on acute myocardial infarction, and its mechanism was related to the inhibition of oxidative stress and the improvement of lipid metabolism disorder.