Periodontitis is a set of inflammatory diseases affecting the periodontium, and the tissues that surround and support the teeth. Mouthwash solutions are mainly used for their antiseptic properties. They currently include synthetic agents, or essential oils. Many natural extracts may also be used, these associate both antiseptic effects and action on host response, due to their antioxidant, immunoregulatory, and analgesic, buffering, or healing properties. The best known are avocado oil, manuka oil, propolis oil, grapefruit seed extract, pycnogenol, Aloe Vera, Q10 coenzyme, green tea, and megamin. AIM: The aim of this study is to assess and compare between the Oral and systemic administration of Aloe Vera on gingivitis Associated with induced periodontits in male Wistar rat. METHODS: Forty adult male Wistar rats with an average weight 150-250 g, 6–7 weeks old were will be assigned to the ligature, and divided randomly into four groups with 10 rats in each group: The first group (control) were daily intraperitoneally injected with saline (5mg/kg). The rats of the second group were given Aloe Vera extract intraperitoneally (300mg/kg) starting one day before ligature and continuing for one month. The rats in the third group were given saline (5mg/kg) orally, while rats in the fourth group were given Aloe Vera extract (300mg/kg) by oral gavage starting one day before ligature and continuing for one month. At the end of 30 days for all groups, all animals were sacrificed, the gingiva was dissected, processed, and a set of sections were stained with haematoxylin and eosin for detection of any morphological changes. The other two sets of sections were labeled for localization of PCNA and caspase-3. The epithelial thickness was measured, and the data were calculated, analyzed and computed to compare the two routes of administration on the induced periodontitis. RESULTS: There was a high significant difference between all groups in their epithelial thickness measurements and high significant difference between the oral and control groups. The immunohistochemistry revealed that there was an overall high significant difference in the PCNA and caspase-3 area% between the studied groups. In addition there has been a high significant increase the PCNA reaction in the oral and intraperitoneal groups versus the control group, while in caspase-3 immunostaining there has been a statistically significant increase in the control group versus both the oral and the peritoneal groups.