Objective：This study aims to investigate the protective mechanism of metformin（Met）on rat cardiomyocytes H9C2 injury induced by lipopolysaccharide（LPS）. Methods：Rat cardiomyocytes H9C2 were divided into Control group，LPS group，Met of different concentrations added with LPS group，according to different treatments. Cells were cultured for 24 hours. MTT was used to detect the cell viability，and intracellular reaction oxygen species and apoptosis were detected by the flow cytometry. The protein levels of Caspase3，BCL2，BAX，t-AMPK（adenosine 5′-monophosphate -activated protein kinase），p-AMPK（phosphorylated adenosine 5′-monophosphate -activated protein kinase），Beclin1 and Parkin were measured by Western blot. Results：Compared with LPS treatment alone，combine of Met and LPS decreased cell viability and apoptosis induced by LPS. The expressions of BCL2 and BAX proteins were decreased，while the Caspase3 protein expression was not decreased. And the expressions of p-AMPK，Beclin1 and Parkin proteins were increased，and the level of reactive oxygen species was deduced. Conclusion：Met may increase autophagy and reduce the production of reactive oxygen species by activating AMPK pathway，alleviate the damage of LPS to cells and protect myocardial cells.