Abstract: To explore the protective effect and possible mechanism of probiotics combined with resveratrol on chronic alcoholic liver injury, C57BL/6J mice were used to construct chronic alcoholic liver injury model. Mice were randomly divided into the control group (Con group), themodel group (Mod group), three intervention groups of probiotics combined with resveratrol (Res) (Lactobacillus paracasei J5+Res (J5+Res), Lactobacillus casei YRL577+Res (YRL577+Res), Bifidobacterium animalis F1-7+Res (F1-7+Res)) groups, and the positive drug tiopronin group (LP group). After the experiment, the liver lipid content, alcohol metabolism enzyme activities, oxidative stress level and other indexes of mice were investigated. In order to further explore the mechanism of the combined action, the mRNA expressions of oxidative stress related genes CYP2E1, nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in liver were analyzed. The results showed that compared with Mod group, probiotics combined with resveratrol could significantly reduce the contents of triglyceride, total cholesterol, serum aspartate aminotransferase and alanine aminotransferase activites in liver of mice (P<0.05), increase the activities of alcohol metabolism enzymes alcohol dehydrogenase and acetaldehyde dehydrogenase in liver, inhibit the activity of CYP2E1 and its mRNA expression in liver. In addition, the contents of glutathione as well as the activities of superoxide dismutase and catalase in liver significantly increased (P<0.05), the Nrf2/HO-1 pathway was effectively activated compared with Mod group (P<0.05). Nrf2 mRNA expression was up-regulated by 2.6, 3.7 and 2.7 times in J5+Res, YRL577+Res and F1-7+Res groups, and HO-1 was up-regulated by 2.0, 6.2 and 4.0 times, respectively. Therefore, probiotics combined with resveratrol mayprevente chronic alcoholic liver injury through the Nrf2/HO-1 pathway.