Objective: To develop and assess a set of criteria to grade inflammation including relative area of inflammation in periapical lesions in endodontically treated teeth. Material and methods: A set of criteria was developed, encompassing data on: Lymphocytes, denoting chronic inflammation, were graded 0 (occasional) to 4 (heavy/dense inflammation). Polymorphonuclear cells, denoting acute inflammation, were graded 0 (none) to 2 (many). The third parameter, area of inflammation, that is, the relative area of the specimen that was inflamed, was graded 0 (none) to 4 (76-100%). The criteria were tested on 199 consecutive biopsies from 180 patients (aged 31-75 years). Information about symptoms was retrieved from the referrals. Mann-Whitney's U-test was used to calculate possible differences in average values for the histopathological variables in the two groups of patients: symptomatic or asymptomatic. Results: Using the criteria, varying grades of inflammation were seen in the biopsies. The majority showed few or no PMN cells. There was a correlation between symptoms and the extent of infiltration of lymphocytes and plasma cells (p ¼ .001), PMN cells (p < .001) and the area of inflammation (p ¼ .002): biopsies from the asymptomatic patients exhibited less pronounced and relatively smaller areas of inflammation. Conclusions: Using the criteria on a specific selection of root-filled teeth with persisting apical periodontitis, periapical inflammation was common, but varied in extent and severity. The inflammation was less pronounced and affected a relatively smaller area in asymptomatic teeth, although outliers in both directions were identified.