The purpose of this investigation was to elucidate the effects of superoxide dismutase (SOD) on the induced periapical periodontitis in rat, and to shed light on the possible mechanism involved in root canal therapy. 48 Wistar rats with induced periapical periodontitis were randomly divided into 3 groups; their root canals of molar teeth were prepared; and the root canals were filled with SOD, CH, and nothing, respectively. At 1, 2, 3 and 5 weeks after operation, 4 animals were killed respectively. Periapical roentgenogram and periapical pathological slices were made. The results were analyzed statistically by F test and t test with SPSS12.0 software package. After root canal therapy, mild inflammatory infiltration was observed in SOD and CH groups at 1 week. At 2 weeks, periapical periodontitis was improved. After 3 weeks, there was no inflammatory cell observed in SOD/CH group. At 3 and 5 weeks, no significant difference in periapical radiographic findings was noted between the experimental groups and normal group (P > 0.05). The periapical radiographic lesion in control group was larger than that in SOD and CH groups (P < 0.01). The results showed that SOD could control periapical inflammation and induce the proliferation of dentin and cementum. Therefore, SOD might be an ideal biocompatible material for root canal therapy.