Abstract: Objective To explore the effects of low concentration (10^-6mol/L) of zoledronic acid (ZA) on osteoclasts and osteoblasts. Methods Osteoclasts and osteoblasts were obtained from neonatal rats and cultured in vitro, and they were divided into control group and ZA group. TRAP staining and image analysis were used to detect the proliferation and activity of osteoclasts. ALP staining and MTT were used to detect the morphological characteristics and proliferation of osteoblasts. Results After a week, osteoclasts showed typical morphological characteristics, and bone resorption lacunas were found in vitro. Compared with control group, the number of osteoclasts and lacunae (P< 0.05), and the area of lacunae (P< 0.05) in ZA group were significantly decreased. Osteoblasts showed typical fusiform and ALP showed positive staining characteristics. The optical density of osteoblasts was dramatically higher in ZA group (3.37±0.11) than control group (2.87±0.12) on day 7 after being cultured, and it had significant difference (P< 0.05). Conclusion The low concentration (10^-6mol/L) of ZA can inhibit proliferation and activity of osteoclasts and promote the proliferation of osteoblasts. Therefore, it is important to choose right administration and dose of ZA to enhance the osteogenesis and inhibit the bone resorption.