Statement of Problem: In most cases of periodontal therapy, antibiotics are suggested as an adjuvant. It is necessary to evaluate the effect of systemic administration of antibiotics in treatment of periodontal diseases and introduce a cost-effective method for management of periodontal infections in individuals who have no access to periodontal therapy.Purpose: This study aimed to compare the effect of antibiotics alone, scaling and root planing (SRP) alone or SRP combined with antibiotics as gold standard approach in improvement of PPD of patients with chronic periodontitis.Materials and Method: This was an experimental study conducted on 44 patients with chronic peridontitis. They were randomly assigned to three groups as follows: 1- SRP Group receiving scaling and root planing alone. 2- AB Group that received antibiotic. 3- Combination Group that received SRP and antibiotic. Clinical measurements including probing depth (PPD), gingival bleeding index (GBI) and plaque index (PI) were performed at base line and 3 months after the treatment. Statistical analyses were performed using covariance analysis kolmogrove-smirnov test and ANOVA test.Results: All 3 groups showed a significant reduction in PPD, GBI and PI 3 months after treatment (p <0.05 in all 3 groups) Improvement in PPD measures in the combination group was statistically significant (p =0.0001). The difference between the groups was not significant with respect to GBI reduction ( p >0.05).Conclusion: In chronic periodontitis, systemic antibiotic therapy alone was as effective as mechanical therapy alone in reduction of PPD, but systemic administration of antibiotic in combination with scaling and root planning showed the most improvement in PPD measuresKey words: Antibiotic, Periodontitis, Scaling