The aim of this study was to evaluate if lidocaine 2% with 1:100.000 epinephrine, used as subgingival irrigation, has anti-inflammatory effect after periodontal therapy. Seventeen patients were selected to this paired split mouth randomized, subject-blind study. Each patient had a minimum of two sites labeled and alleatory separated, both with probe depth ≥ 5 mm. Each site were separated in two groups: scaling and root planing + lidocaine 2% with 1:100.000 epinephrine used as subgingival irrigation (LD); and scaling and root planing + saline solution (SRP), both groups were blinded to the examiner. Clinical periodontal parameters were recorded: plaque index (PI), bleeding on probe (BOP), probing depth (PD), gingival recession (GR) and clinical attachment level (CAL). Levels of GCF-PGE 2 were analyzed by enzyme-linked immunosorbent. All parameters were recorded at baseline (1 and 3 months) after periodontal treatment. The results indicated reduction of PI, BOP, PD, CAL for LD and SRP groups and GCF-PGE 2 levels were reduced in LD group after 3 months periodontal therapy. The LD and SRP groups were equally efficacious to control the periodontal disease after 3 months. However, LD improved the reduction of PGE 2 levels and maintains the inhibitory anti-inflammatory effect on PGE 2 after 3 months of periodontal treatment.