Background: Lipopolysaccharide (LPS) endotoxins are activators of innate immunity inducing infection and inflammatory responses. Anti-inflammatory drugs can have undesirable side effects. Acupuncture may be an alternative for the treatment of inflammatory processes. Objective: We investigated the potential anti-inflammatory effect of manual acupuncture (MA) at SP6 upon LPS-induced peritonitis in rats. Methods: Peritonitis was induced in rats with an intraperitoneal injection of LPS (0.002, 0.02, 0.2 or 2 µg/kg) in four experimental groups (n = 6 each). A fifth group was injected with sterile saline solution (saline group, n = 6). Four hours after the procedure, peritoneal fluid was collected to determine total cell counts for inflammatory cells, differential leukocyte counts and peritoneal capillary permeability. The LPS dose of 0.02 µg/kg was used in the subsequent experiments as it most successfully induced peritoneal inflammation. Subsequently, five experimental groups (n = 12 rats each) were used: (1) saline, (2) control (untreated LPS group), (3) indomethacin (LPS group treated with indomethacin), (4) NA (LPS group treated with MA at a location not corresponding to any traditional acupuncture point), and (5) SP6 (LPS group treated with verum MA at SP6). Ten minutes after MA or 30 min after indomethacin treatment, the rats received an intraperitoneal injection of LPS. After 4 h, total leukocyte and differential cell counts, myeloperoxidase (MPO) activity, vascular permeability and cytokine levels were evaluated in the peritoneal fluid. Cytokine levels were additionally evaluated in the brainstem. Results: SP6 MA and indomethacin treatments reduced inflammatory cell infiltration, vascular permeability and MPO activity in the LPS-exposed rats. Pre-treatment with indomethacin and SP6 MA decreased tumor necrosis factor (TNF)-α levels and preserved interleukin (IL)-10 in the peritoneal fluid. Indomethacin also reduced IL-6 in the peritoneal fluid. In the brainstem, indomethacin reduced IL-1β, IL-6, TNFα and IL-10, whereas SP6 MA reduced only TNFα and IL-6 levels. Conclusions: This study clearly demonstrates the anti-inflammatory effect of acupuncture, which we believe may involve the activation of anti-inflammatory neural reflexes in the regulation of peritonitis.