Objectives: Superoxide is an oxygen radical released in inflammatory pathways (arachidonic acid metabolism) that cause tissue destruction, while superoxide dismutase (SOD) is an antioxidant enzyme that acts against this radical. Since, non-steroidal anti-inflammatory drugs (NSAIDs), adjunctive to periodontal treatment can inhibit prostaglandin and oxygen radical synthesis, this study aimed to evaluate gingival and gingival crevicular fluid (GCF) SOD levels in chronic periodontitis (CP), and value of ibuprofen (Artril) treatment and flap surgery. Methods: All patients (n=26) received flap surgery following ibuprofen (Artril) treatment (3x 400 mg/day, 6 weeks).Before ibuprofen treatment; samples were obtained (GCF before, gingiva during surgery) from one maxillary quadrant (Site A). After ibuprofen treatment; same samplings were performed at the contralateral quadrant and in additon GCF sampling was repeated at post-operative 1 and 3 months (Site B). In controls (n=18), GCF and gingival samples were obtained from premolars extracted for orthodontic reasons. Clinical measurements were performed at all time points. SOD activity was determined spectrophotometrically and data was statistically analyzed. Results: Gingival SOD activity was higher in CP than controls (p<0.05) while GCF presented no significant difference (p>0.05). After ibuprofen treatment, while SOD significantly decreased in gingiva (p<0.05), GCF revealed no significant change (p>0.05) . Gingival SOD, following drug treatment was significantly higher than controls (p<0.05). GCF SOD activity did not significantly change at post-operative 1 and 3 months from baseline (p> 0.05). However, a significant elevation at 3 months compared to 1 month was observed (p<0.05).No significant correlation was observed between gingival and GCF SOD activity (p<0.05). Conclusion: When compared to GCF, gingival SOD may be prominently affected both by periodontal disease and treatment. NSAID treatment may reduce the need for SOD production in gingiva. It may be speculated that GCF and gingival SOD tend to act in distinct manners. (Partially supported by Eczacýbasi Incorporation).