Periodontitis is an inflammatory infection of the periodontal tissue that, if left untreated, may result in tooth loosening and ultimate tooth loss. The goal of our research is to see the efficacy of minocycline microspheres (Arestin) in treating chronic periodontitis. In this study, forty chronic periodontitis patients (17 males and 23 females) between the ages of 20 and 45 were included. Patients were randomly allocated into two groups. Group I: (Test group) contained 20 patients who were treated with scaling and root planning (SRP) with Arestin (Minocycline HCl microspheres). Group II: (Control group) included 20 patients who were treated with scaling and root planning (SRP) only. For microbiological study samples were collected before treatment (baseline) and on days 30, 90, and 180 after treatment in both groups for platting on nonselective Anaerobic Thioglycolate Medium Base (ATMB) agar plates supplemented with horse serum (5%) and kanamycin-vancomycin-bacitracin, which is employed for the selective recovery of obligatory anaerobic Gram-negative rods for colony forming unit calculations. A Multiplex PCR was used to amplify the bacterial DNA from Aggregatibacter actinomycete mcomitans (A.a.), Tannerella forsythia (T.f.), and Porphyromonas gingivalis (P.g.) Treponema denticola (T.d.). Microbiological analysis was significantly lower in groups I and II. Scaling and root planing with Arestin (minocycline hydrochloride microbeads) can be considered as a new and effective treatment for patients with chronic periodontitis.