Inflammation and oxidative stress are biological processes that cause tissue damage in animals. An increasing number of studies have highlighted the broad prospects of probiotics in improving inflammation and oxidative stress, but the mechanism of Lactobacillus acidophilus (LA) in alleviating the inflammatory/oxidative response is unclear. In this study, we used Salmonella typhimurium (ST)-infected mice as a pathogenic model, and explored the role of LA in alleviating the inflammatory/oxidative response based on the p62-kelch-like ECH-associated protein-1 (Keap1)-NF-E2-related factor 2 (Nrf2) signaling pathway and cecum microbiota. After 14 d of treatment with LA, mice were infected with ST for 24 h.