Objective：This study aims to observe the protective effect of periodontitis gene vaccine pVAX1-HA2-FimA and pVAX1-HA2-FimA/IL-15 in SD rats with experimental periodontitis. Methods：Fifty-four male SD rats were randomly divided into 9 groups：Control group（normal saline group，group A），empty plasmid pVAX1 group（group B），periodontal disease group（group C），Experimental group［50 μg，100 μg，150 μg pVAX1-HA2-FimA group（D，E，F group）and 50 μg，100 μg，150 μg pVAX1-HA2-FimA/IL-15 group（G，H，I group）］. Experimental periodontitis model was established after nasal drip immunization of SD rats，and the relative expression levels of TNF- α and MMP-8 mRNA in gingiva were detected by RT-qPCR. The absorption of alveolar bone was observed and measured by stereomicroscopy. Results：①The TNF-α and MMP-8 mRNA in the gingival tissues of each experimental group were lower than that in the periodontal disease group，and the differences were statistically significant（P < 0.05）. ②Compared with the pVAX1-HA2-FimA group，the amount of alveolar bone absorption in the pVAX1-HA2-FimA/IL-15 group with the same vaccine dose was lower，and the differences were statistically significant（P < 0.05）. Conclusion：The periodontitis gene vaccines pVAX1-HA2-FimA/IL-15 and pVAX1-HA2-FimA have protective effects on SD rats with experimental periodontitis.