Abstract: Objective To investigate the effect of epoxy resin paste for root canal filling in the treatment of pulp disease and periapical periodontitis. Methods A total of 60 patients with pulpopathy and periapical periodontitis treated in our hospital were randomly divided into control group and study group, given root canal filling therapy in both groups. The control group(n=30)was treated with blue root filling paste and guttapercha filling in combination, while the study group(n=30)was treated with epoxy resin paste combined with gutta-percha filling. The serum levels of interleukin-4(IL-4), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and high-sensitivity C reactive protein(hs-CRP)were compared before and after treatment. The Visual Analogue Scale(VAS)score was used to compare the pain of the two groups before and after treatment, and the clinical efficacy of the two groups was evaluated. Results There were no significant differences in the levels of IL-4, IL-6, TNF-α and hs-CRP between the two groups before treatment(P>0.05), the levels of IL-4 were increased after treatment, and levels of IL-6, TNF-α and hs-CRP were significantly decreased after treatment(P<0.05), and the levels of IL-4, IL-6, TNF-α and hs-CRP in the observation group were significantly improved than those in the control group, the difference was statistically significant(P<0.05). The VAS score of the observation group was significantly lower than that of the control group on the 7^th and 28^th postoperative day(P<0.05). The clinical excellent and good rate of the observation group was 93.33%, which was significantly higher than 73.33% of the control group(P<0.05). Conclusion Epoxy resinpaste can be used as an ideal material for root canal filling in - the treatment of pulp disease and periapical periodontitis, which has significant effects on inhibiting inflammatory reactions and reducing pain of patients.