Objective To investigate the effects of substance P on cultured rat osteoclasts. Methods Neurokinin-1(NK1)receptor expression in osteoclasts was examined by immunohitochemical method, and changes of bone resorption activity caused by substance P and NK1 receptor antagonists were detected by pit formation assay. Results Immunoreactivity for NK1 receptor was distributed in the cytoplasm of osteoclasts. The average of pit formation areas significantly increased with addition of substance P (10-7-10-4 mol/L) (P0.05). NK1 receptor antagonists inhibited the enhancement of the bone resorption by substance P addition. Conclusion The findings suggested that substance P may stimulate osteoclasts and result in bone resorption by the mediation of NK1 receptor.