The present study was performed to assess and compare the clinical and microbiological effects following local application of 2% minocycline gel or 0.1% chlorhexidine subgingival irrigation to augment scaling and root planing in patients with moderate to advanced chronic adult periodontitis. 32 healthy patients with moderate to advanced chronic adult periodontitis were enrolled in the study. In each patient, the quadrants that had 2 or more teeth with $5{sim}8mm$ probing pocket depth and radiographic evidence of alveolar bone loss were selected and divided into test side and control side according to the split-mouth design. All patients received standardized oral hygiene instructions at the beginning of the study and all remaining teeth received scaling and root planing until 0 week. The 2% minocycline gel was applied to periodontal pocket at 0, 1, 2, 3 week in the test side. The 0.1% chlorhexidine solution and the normal saline were irrigated subgingivally for about 30 seconds in the positive control side and negative control side respectively. The clinical and microbiological analysis carried out at 0, 4, 8, and 12 weeks . The results of this study were as follows; 1. In saline irrigation group, there was no adjunctive effects in probing pocket depth reduction, sulcular bleeding index and no significant changes in relative proportions of subgingival bacteria. 2. The chlorhexidine irrigation as an adjunct to scaling and root planing results in reduction in the plaque index and sulcular bleeding index, but there was not statistically significant. The relative proportion of spirochetes was significantly reduced, but the proportion of motile rods was no significant reduction. 3. The minocycline gel delivered subgingivally as an adjunct to scaling and root planing provide significant benefit in reducing probing depths and sulcular bleeding index compared to saline and chlorhexidine irrigation groups. 4. The relative proportions of spirochetes and motile rods were significantly reduced and the proportions of cocci and non-motile bacteria were correspondingly increased in the minocycline gel group. In conclusion, minocycline gel delivered subgingivally as an adjunct to scaling and root planing induces clinical and microbial responses more favorable for periodontal health than saline and chlorhexidine subgingival irrigation.