Abstract: Objective To investigate the pathogenesis and treatment of recurrent aphthous ulcer, and to discuss the therapeutic effect of rehabilitation new fluid combined with ozone, and to discuss salivary epidermal growth factor (EGF) and serum interleukin-6. The effects of (IL-6), superoxide dismutase (SOD), and secretory immunoglobulin A (sIgA) were investigated. Methods Sixty-four patients with recurrent aphthous ulcer admitted to our hospital from January to February 2018 were randomly divided into two groups. The control group was treated with ozone. The study group was applied on the basis of the control group. Rehabilitation new fluid treatment. The changes of IgG, SIgA, SOD, VAS score, ulcer duration and serum level were compared before and after treatment. Results The changes of IgG and SIgA in the study group were significantly higher than those in the control group (all P<0.05). The IgG, SIgA and SOD values of the study group were (23.5±6.4) g/L, (64.6±11.2) g/L and (290.2±57.3 ) g/L, respectively. The difference was statistically significant. The VAS score (2.01±0.23) and the ulcer persistence score (3.25±0.96) were lower in the study group than in the control group (all P<0.05).The TNF-α, IL-6 and EGF indexes in the study group were respectively determined. The scores were (134.02±20.15) ng/mL, (73.23±8.73) ng/mL and (3.2±0.6) ng/mL, which were lower than the control group (all P<0.05). The difference was statistically significant. Conclusion For patients with recurrent aphthous ulcer, the treatment of rejuvenating new fluid combined with ozone is not only effective, but also promotes the regeneration and repair of damaged epidermis, effectively improving the saliva EGF of patients and serum IL-6, SOD, sIgA levels.