Abstract: AIM: To search for osteostatin(OSN) analogues with enzymatic stability as the promising candidates for developing new anti-osteoporosis drug.METHODS: Target compounds were synthesized on the BNR resin with pooling strategy, and their bioactivities were evaluated in vivo by determining the body weight, fractures, femoral dry weight, femoral diameter, and the numbers of integral femur in rats. RESULTS: Three (g,i and r) of twenty one analogues were found to be as active as OSN. CONCLUSION: Both residues at N and C terminal in OSN molecule could be changed properly without losing the original bioactivity. Therefore, it is possible to develop some ideal OSN surrogates with higher bioavailability as the candidate for anti-osteoporosis drug.