OBJECTIVE： To study the effect of catalpol on the activity and apoptosis of osteoclasts （OC） in the osteoblasts （OB）-OC co-culture system and its mechanism. METHODS： OB and OC were isolated respectively from the SD rats of 1-3 days and 5-7 days old to establish OB-OC co-culture system. After treated with 0 （blank control）， 0.05， 0.5， 5， 50 and 100 mg/L catalpol for 48， 72 and 96 h， the number of bone absorption lacuna for OC was observed by inverted microscope to reflect OC activity. After treated with 0 （blank control） and 0.05 mg/L catalpol for 48， 72 and 96 h， the activity of tartrate resistant acid phosphatase （TRACP） in OC was detected， and the apoptosis rate of OC was calculated. After treated with 0 （blank control） and 0.05 mg/L catalpol， mRNA expression of osteoprotegerin （OPG） in OB was detected. RESULTS： In OB-OC co-culture system， the number of bone absorption lacuna in 0.05-50 mg/L catalpol groups was significantly lower than blank control group （P＜0.01）， indicating catalpol could inhibit OC activity， especially 0.05 mg/L catapol. Compared with blank control， 0.05 mg/L catapol lowered the activity of TRACP but increased the apoptosis rate of OC （P＜0.05）； mRNA expression of OPG was up-regulated in OB （P＜0.01）. CONCLUSIONS： In OB-OC co-culture system， catalpol can inhibit the activity of OC and induce the apoptosis of OC， and its mechanism may be associated with the mRNA expression up-regulation of OPG in OB.