Introduction: Overproduction of gingival pro-inflammatory cytokines have been implicated to play a noticeable role in the pathogenesis of periodontitis, which is characterized by host-mediated destruction of soft and hard periodontal tissues. Moringa oleifera (MO) is a highly valued medicinal plant which has a wide impressive range of traditional medical applications and is an alternative medicine for synthetic drugs which are accompanied with many downsides. The aim of this study was to investigate the effect of administration of the MO extract on gingival levels of TNF-α and IL1-β in the rat periodontal model. Methods: Inflammatory periodontitis was induced using 0-3 ligatures around the neck of right mandibular first molar in male rats. MO leaf extract was solved in dimethyl sulfoxide and injected into the gum tissue directly (500mg/kg) as a pre/post-treatment. Positive control group gave indomethacin (5mg/kg) on a daily basis. Gingival levels of TNF-α and IL1-β were measured using ELISA. Results: The results of this study revealed that levels of IL1-β and TNF-α increased in the gingival tissue in a model of periodontitis compared to control group (P≤0.001). Also, the results indicated that administration of MO extract could reduce production of TNF-α and IL1-β in the gum tissue of rat periodontal model (P≤0.001). There was no significant difference between MO extract and indomethacin anti-inflammatory effects. Conclusion: It can be concluded that pre/post-treatment with MO extract due to its direct effect on inhibition of pro-inflammatory cytokines can alleviate inflammatory symptoms in a rat periodontal model.