At present, the pathogenesis of sepsis-induced myocardial dysfunction (SIMD) is not completely clear and effective treatment measures are lacking. Apelin is an endogenous ligand of the angiotensin like G protein coupled receptor APJ and a cardiovascular peptide with multiple functions. Our aim is to analyze the protective effect and mechanism of Apelin/APJ system on lipopolysaccharide (LPS)-induced myocardial dysfunction. One hour before LPS treatment, apelin-13 or an APJ antagonist [Ala]-apelin-13 (F13A) was given for pre-intervention to observe the effect of apelin-13 on cardiac ultrasound, pathological changes and inflammatory factors in LPS-treated mice. Another part of the mice was treated with apelin-13 or apelin-13 combined with F13A one hour after LPS treatment. The results showed that apelin-13 injection significantly reversed the decrease of ejection fraction and the increase of inflammatory factors induced by LPS in mice. Endogenous apelin may have protective effect on SIMD induced by LPS. Exogenous administration of apelin may inhibit LPS-induced inflammation, apoptosis and increase autophagy through TLR4/ERK1/2/NF-κB pathway.