Periapical lesions are inflammatory diseases that extend following bacterial canal infection. In this study, we are looking for the role of prophylactic ibuprofen and N-acetylcysteine on the levels of TNF- α and IL-6 in chronic periapical lesions. Periapical radiographs are taken using bisecting technique and patients with radiolucencies less than 1 cm are randomly assigned to one of following four groups to receive ibuprofen 400 mg, NAC600 mg , Ibuprofen 200+NAC600 mg, or placebo (starch). Medications are made using 500 mg gelatinous capsules. The pain severity is recorded using visual analog scale (VAS). Each patient receives 2 similar capsules 2 hours and 30 minutes prior sampling. Then, the patient is anesthetized, the tooth is isolated and the access cavity is provided. Canal preparation is done up to size #40 file for single rooted teeth and size #30 file for multi-rooted teeth. Irrigation with normal saline is done and the canal is dried with paper points. Two paper points with size 30 are inserted in the canal and each kept in place for 30 seconds for exudates sampling. For teeth with active drainage, the points are kept with shorter time. If blood is observed, the sample is excluded, and if the point is dry, a fine file (size 8 or 10) passes the foramen and lets the exudates come into the canal. The wet length of the paper point is recorded and the volume of the fluid is calculated using Shimauchi standard curve in μl. the point is inserted in a microtube containing phosphate buffered saline (PBS) with 0.05% twin 20. They are vortexed for 1 minute, and centrifuged, and the supernatant is isolated and kept in-70̊ C. VAS is repeated 4, 8, 12 and 24 hours later. Samples are analyzed using ELISA and cytokine levels are compared between groups.