〔Abstract〕 Objective To investigate the effects of milk derived pentapeptide prolin-glycine-proline-isoleucine-proline(PGPIP) on chronic alcoholic liver injury in mice and its related molecular mechanism. Methods Forty C57BL/6 mice were randomly divided into control group, model group, glutathione(GSH) group, PGPIPN group. The mice model of chronic alcoholic fatty liver was established by 10 d ad libitum oral feeding with the Lieber-DeCarli(LD) ethanol liquid diet plus one binge. Drug intervention was given at the same time. Based on the reported RNA sequencing data in gene expression omnibus(GEO) database, the differential expression of liver endoplasmic reticulum stress-related genes was analyzed by cluster heat map. Liver hematoxylin-eosin(HE) staining was used to analyze the pathological effects of each treatment group on alcoholic liver injury in mice. Oiled Red O staining was used to analyze the effects of each treatment group on the accumulation of liver lipid droplets in mice. Transmission electron microscopy was used to analyze the effect of lipid droplet accumulation caused by alcohol metabolism on the microstructure of hepatocytes and verify the effect of PGPIP. Endoplasmic reticulum stress-related signal transduction protein expression was detected by Western blot. Results The pathological examination of PGPIP group was similar to that of Control group, and the liver injury of mice was significantly reduced. The accumulation of lipid droplets in the liver of mice in the model group was manifested as mixed lipid droplets of different sizes, and PGPIP treatment significantly reduced the accumulation of liver lipid droplets induced by alcohol. PGPIP had significant effects on the PERK-eIF2α-ATF4 pathway and the expression of transcriptional activator 6(ATF6), Cleaved Caspase 3 protein. Conclusion Pentapeptide PGPIP can alleviate chronic alcoholic fatty liver and liver injury in mice. The mechanism may be attributed to reducing the accumulation of lipid droplets in hepatocytes, endoplasmic reticulum stress, and hepatocyte apoptosis.