Cyclosporine A (CsA), broadly used in organ transplantation, may contribute to pathogenesis of osteoporosis. The aim of this study was to investigate the effects of CsA on alveolar bone in rats subjected or not to experimental periodontal disease using biochemical, radiographic, and histometric analysis. Forty Wistar rats were divided into 4 equal groups: Group I (Control), Group II (CsA was injected subcutaneously in a daily dose of 10 mg/kg), Group III (Ligature was placed around the mandibular molars), Group IV (Ligature+CsA). After 60 days, rats were decapitated, serum alkaline phosphatase and calcium levels were measured. Radiographic-alveolar bone loss (ABL), histometric-ABL, and percentage of new alveolar bone formation (NABF%) were determined on mandibular molars. Significant increase in serum alkaline phosphatase levels (p < 0.001), no significant difference in calcium levels were observed (p > 0.05) in Group IV compared to Group III. Radiographic and histometric-ABL were significantly less (p < 0.001), NABF% was significantly greater (p < 0.05) in Group IV than in Group III. No significant difference in any of the parameters between Group II and Group I was found. It can be concluded that in the presence of periodontal disease, CsA treatment may bring out an imbalance in the alveolar bone homeostasis by decreasing resorption and stimulating formation of alveolar bone in rats.