Introduction: Aggressive periodontitis is a specific type of periodontal disease that is characterized by rapid attach-ment loss and bone destruction resulting in tooth loss. Graptophyllum pictum (L.) Griff is a vine that is widely used as a herbal medicine in Indonesia. Graptophyllum pictum (L.) Griff contains flavonoids, steroids, tannins, coumarins, saponins, anthtraquinones, phenols, and sugar. It is known that flavonoids contains quercetin which is known to have anti-inflammatory activity. The aim of this research was to investigate the effect of Graptophyllum Pictum (L.) Griff. extract gel on the number of macrophages as an inflammatory indicator on periodontal tissue of Wistar (Rattus norvegicus) rats with periodontitis. Methods: Twenty-four male Wistar rats were randomly divided into 5 groups: negative control group, positive control group and treatment group treated with 7.5%, 15%, and 30% Graptophyl-lum Pictum (L.) Griff. extract gel for 3 days. The periodontitis was induced by 0.2 ml Aggregatibacter actinomycetem-comitans (Aa) 109 CFU on the right lower molar gingival sulcus, three times a week. The number of macrophages from gingival tissue was analyzed by hematoxylin-eosin staining for histopathologic examination. Results: The num-ber of macrophages (mean + SD) were 1.50 + 0.577 in negative control group; 10.25 + 2.062 in positive control group; 5.00 + 2.530, 3.76 + 1.211, 2.50 + 1.975 in treatment group with 7.5%, 15%, and 30% respectively. The significant difference in the average number of macrophages between the negative control group compared with the positive control indicates that the number of macrophages in the inflammatory process was increased to overcome Aa bacteria. In the treatment group, the number of macrophages was lowest at 30%, followed by 15%, and 7.5% of Graptophyllum pictum (L.) Griff extract gel. Conclusions:Graptophyllum Pictum (L.) Griff. extract gel can decrease the number of macrophages in Wistar rats with periodontitis. The concentration of 30% Graptophyllum Pictum (L.) Griff. extract gel was the most effective concentration in decreasing the number of macrophages.