Lactobacillus paracasei ET-22 is a kind of probiotic that can relieve intestinal inflammation and regulate immune functions, but the effects on oral diseases and its mechanism need to be further studied. In this study, an oral ulcer model based on golden hamster was established by buccal injection of methyl viologen, and the effects of ET-22 on the phenotype of oral ulcer and the inflammatory factors expression level were studied through previously treating hamsters with 1×10⁹CFU/mL/day of live ET-22, inactivated ET-22 and fermented broth of ET-22. The results based on histopathological section observation and score of oral mucosa showed that the intervention of live ET-22, inactivated ET-22 and its fermented broth could improve the epithelial integrity and inflammatory cell infiltration of oral mucosa in oral ulcer model hamsters. And the live ET-22 had the best performance on prevention of oral ulcer, followed by inactivated ET-22 and fermented broth of ET-22, but their effects were all better than the effect of vitamin C intervention. On the one hand, ET-22 could inhibit the secretion of pro-inflammatory cytokines IL-6 and IL-1β by down-regulating the expression of NF-κB, thereby reduced the expression of matrix metalloproteinase MMP-9 and alleviated the inflammatory infiltration and metastasis of oral mucosa. On the other hand, ET-22 could regulate oral microbiota composition and inhibit harmful bacteria related to oral diseases. The study indicated that ET-22 could decrease the risk of oral ulcer and play a positive role in the prevention of oral ulcer.