Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 07 11 1 13 Ya Hu Department of Stomatology, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology, The Second Clinical Medical College, Jinan University), Shenzhen, China Lanlan Zhu School of Clinical Medicine, Chongqing Medical and Pharmaceutical College, Chongqing, China Hanyan Li Department of Stomatology, Zhuanqiao Community Health Service Center, Shanghai, China 2025 12 24 2026 02 12 Periodontitis is a chronic inflammatory disease driven by dysregulated immune responses to microbial biofilms, in which excessive pro-inflammatory cytokine production contributes to periodontal tissue destruction. Although laser-assisted periodontal flap surgery has been proposed as an adjunctive therapy, its effects on inflammatory mediator regulation remain unclear. This meta-analysis evaluated the effects of laser-assisted periodontal flap surgery on tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP), and their association with clinical outcomes in patients with Stage 3–4, Grade B/C chronic periodontitis. Randomized controlled trials comparing laser-assisted periodontal flap surgery with conventional flap surgery were systematically retrieved from major English and Chinese databases. Primary outcomes included changes in inflammatory biomarkers measured in gingival crevicular fluid or serum; while probing depth (PD), clinical attachment level (CAL), gingival index, and postoperative pain were secondary endpoints. Meta-analyses used fixed- or random-effects models according to heterogeneity, with sensitivity analyses conducted to assess result robustness. Twelve randomized controlled trials were included. Laser-assisted therapy significantly reduced early postoperative (24-hour) TNF-α (MD=−0.88, 95% CI −1.01 to −0.75) and IL-6 (MD=−1.41, 95% CI −1.81 to −1.02) compared with conventional surgery, while CRP showed no significant difference. Clinically, adjunctive laser therapy improved short-term probing depth reduction at 3 and 6 months, whereas CAL improvements were not consistently sustained. Laser-assisted periodontal flap surgery significantly downregulates key inflammatory cytokines in the early postoperative period and may improve short-term outcomes. However, long-term periodontal attachment stability remains uncertain, warranting further well-designed studies with standardized biochemical and clinical assessments. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4719 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4719/2355