ObjectiveTo explore the improvement and mechanism of the water extract of Lonicerae Japonicae Flos （FL） on nonalcoholic steatohepatitis （NASH）. MethodC57BL/6 mice were fed with methionine-choline-deficient （MCD） diet for 6 weeks. From the 3^rd week， the mice were continuously orally given with FL （0.2 and 0.4 g·kg^-1） until the end of the experiment. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities of mice were detected， and the liver pathology was analyzed by hematoxylin-eosin （HE） staining. The content of triglyceride （TG） and non-esterified fatty acids （NEFA）， and the activity of myeloperoxidase （MPO） in the liver tissue were determined. Hepatic collagen deposition was observed by Sirius Red and Masson staining assays， and the hepatic hydroxyproline （HYP） content was measured. Network pharmacology combined with following experimental verifications were used to analyze the potential mechanism of FL in the improvement of NASH. Real time polymerase Chain reaction （Real-time PCR） was used to detect hepatic mRNA expression of inflammation-related factors and fibrosis-related factors. The release of heat shock protein （HSP60） in the serum and α-smooth muscle actin （α-SMA） in the liver were detected by Western blot. ResultFL （0.2 and 0.4 g·kg^-1） reduced serum ALT and AST， hepatic MPO activity， and HYP content in the MCD-induced NASH mice. The results of network pharmacology suggested that FL presumably improved NASH by influencing biological processes related to extracellular matrix and inflammation， and signal pathways such as nuclear factor kappa-B （NF-κB）， hypoxia inducible factor-1α （HIF-1α）， and heat shock proteins were possibly involved. FL （0.2 and 0.4 g·kg^-1） reduced the increase of mRNA expression of inflammation-related and fibrosis-related factors， and FL （0.4 g·kg^-1） decreased the release of HSP60 in serum and reduced the protein expression of α-SMA in liver. ConclusionFL improves NASH by reducing inflammation， decreasing collagen deposition， and inhibiting HSC activation.