Abstract: Objective: To analyze the effects of hyperbaric oxygen on the serum levels of substance P(SP), prostaglandin E2(PGE2) and inflammatory factors in patients with trigeminal neuralgia. Methods: A total of 90 patients with trigeminal neuralgia were selected as the research subjects, and randomly divided into the observation group and control group(45 cases in each group).The control group was treated with carbamazepine by oral administration combined with block therapy, and the observation group were treated with hyperbaric oxygen on the basis of the control group.The treatment effect between two groups was compared, and the serum levels of SP, PGE2 and inflammatory factorinterleukin-1β(IL-1 β), interleukin 6(IL-6) and tumor necrosis factor-α(TNF-α) before and after treatment, scores of pain visual analog scale(VAS), European five-dimensional health scale(EQ-5D) and adverse reactions were compared between two groups. Results: The total effective rate in the observation group was 93.33%, which was significantly higher than that of control group(77.78%)(P < 0.05).After treatment, the levels of SP and PGE2 in two groups decreased compared with before treatment(P < 0.05), and the levels of SP and PGE2 in the observation group were lower than those in control group(P < 0.01).After treatment, the levels of IL-1β, IL-6 and TNF-α in two groups decreased compared with those before treatment(P < 0.05), and the levels of IL-1β, IL-6 and TNF-α in the observation group were lower than those in control group(P < 0.01).After treatment, the VAS scores in two groups were lower than that before treatment(P < 0.05), and the EQ-5D scores in two groups were higher than that before treatment(P < 0.05).After treatment, the VAS score in the observation group was lower than that in control group(P < 0.05), and the EQ-5D score was higher than that of in control group(P < 0.05).There was no statistical significance in the incidence rates of adverse reactions between two groups(P>0.05). Conclusions: Combined with hyperbaric oxygen on the basis of conventional treatment can significantly improve the therapeutic effect of patients with trigeminal neuralgia, further regulate the body′s immune and inflammatory response, reduce the degree of pain, improve the quality of life, and there is no obvious adverse reactions, it is worthy of clinical promotion.