Periodontitis is a major risk factor in the oral cavity in chronic diabetes mellitus. The level of IL-1β as inflammatory cytokine increased in patients with type 2 diabetes and periodontitis, while IL-10 is an anti-inflammatory cytokine, may mediate periodontitis in diabetes. Stichopus hermanii (SH) have been known to have anti-inflammation property. Hyperbaric Oxygen Therapy (HBOT) thas been used as adjuvant therapy in diabetes wound healing. To examine the effect of combination SH and HBOT to the expression of inflammatory response of IL-1β and IL-10 on diabetic periodontitis rats. Thirty male Wistar rats were divided to normal (K-0), diabetic-periodontitis (K-1), and treatment group of SH (K-2), HBOT (K-3), and SH-HBOT (K-4). Experimental diabetic was induced by single dose 65 mg/kg of BW intraperitoneal. The Sticopus hermanii gel 3% by topical application in sulcus gingiva and HBOT 2, 4 ATA 3x30 minutes interval 5 minute for 7 days. After 52 days the animals were decapitated and the expression of IL-1β and IL-10 were examined by immunohistochemistry. Data were analyzed with ANOVA and LSD. The expression of IL-1β were raised in K-1 group (10.68±1.50)(p< 0.05), while IL-10 were not raised (8.00±1.95) compare to normal group (7.25±0.85)(p> 0.05). Treatment with SH in K-2 group resulted in decreased of IL-1β expression (10.00±1.09) while the expression of IL-10 were raised (8.33±2.60) compare to K-1 (7.25±0.85)(p< 0.05). Treatment with HBOT in K-3 group resulted in decreased of IL-10 expression (8.333±0, 81) while the expression of IL-10 were raised (10.67±1.03) compare to K-1 (p< 0.05). Treatment with SH-HBOT in K-4 group showed the most decreasing expression of IL-1β (6.50±2.44) and increasing expression of IL-10 (14.83±1.47) compare to K-1 (p< 0.05). Combination of SH-HBOT decreased the expression of IL-1β and increased the expression of IL-10 on diabetic periodontitis diabetes rats