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Objectives Studies have reported that whole body vibration (WBV) played a vital role in bone remodeling.Circulating serotonin has been demonstrated to be involved in negative regulating bone mass in rodents and humans.However, both WBV and inhibition of serotonin biosynthesis could suppress RANKL-induced osteoelastogenesis in vitro.Current study is to investigate the effect of WBV therapy on the expression of serum serotonin in ovariectomized rats.Materials and Methods Thirty 6-month-old female Sprague Dawley rats were ovariectomized to induce osteoporosis, and another ten rats underwent sham operation to establish sham control (SHAM) group.After 3 months, ovariectomized rats were divided into three subgroups and then separately treated with WBV, Alendronate (ALN) and normal saline (OVX), SHAM group was given normal saline.Treatment was given for another 6 weeks.After sacrificing the rats, blood and femur samples were collected for serum serotonin, RANKL, bone turnover markers assay, and bone mineral density (BMD), bone strength analysis.Results Mter 6 weeks of treatment, the serum serotonin level was significantly lower in WBV group than OVX and ALN groups (p < 0.05 and p < 0.001).RANKL levels significantly decreased in WBV and ALN groups compared to OVX group (p < 0.001 for both).BMD and biomechanical parameters of femur significantly increased (p < 0.05 for both) and bone turnover levels decreased (p < 0.001 for both) in WBV group compared to OVX group.Conclusion These data indicated that WBV enhanced bone strength and BMD in ovariectomized rats most likely by reducing the expression of Circulating serotonin.