Obesity is primarily caused by the excessive accumulation of white adipose tissues(WAT). We previously obtained an adipocyte-specific aptamer termed Adipo8 in vitro. In this present study, this adipocyte-specific aptamer Adipo8 was first chemically modified by introduction of phosphorothioate linkages(PS-linkages) and then conjugated to polyethylene glycol(PEG), we tested whether this modified aptamer could distinguish mature white adipocytes from 3T3-L1 preadipocytes or brown adipocytes. To verify the binding affinity of this aptamer to mature white adipocytes in vivo as well as in vitro, we tested whether modified Adipo8 could specifically bind to the WAT of Diet-Induced Obesity(DIO) C57BL/6 mice. Finally, we examined the effect of Adipo8 on the adipogenic differentiation of mature white adipocytes. Based on our results, PS-modified aptamer demonstrated its high binding affinity and specificity, and was able to distinguish white adipocytes from 3T3-L1 preadipocytes or brown adipocytes in vitro. PS-modified Adipo8 also demonstrated more biostability and prolonged binding time in biological fluids. Additionally, Adipo8 could inhibit adipogenic differentiation of adipose tissue, possibly by inhibiting the expression of PPAR-γ in adipose tissue. This modified aptamer holds great promise as a stable molecular recognition tool for targeted delivery to adipocytes and has potential in the treatment of obesity. Obesity is therefore caused by the excessive accumulation of white adipose tissues (WAT). We previously obtained an adipocyte-specific aptamer termed Adipo8 in vitro. In this present study, this adipocyte-specific aptamer Adipo8 was first chemically modified by introduction of phosphorothioate linkages ( PS-linkages) and then conjugated to polyethylene glycol (PEG), we tested whether this modified aptamer could distinguish mature white adipocytes from 3T3-L1 preadipocytes or brown adipocytes. To verify the binding affinity of this aptamer to mature white adipocytes in vivo as well As in vitro, we tested whether modified Adipo8 could specifically bind to the WAT of Diet-Induced Obesity (DIO) C57BL / 6 mice. Finally, we examined the effect of Adipo8 on the adipogenic differentiation of mature white adipocytes. Based on our results, PS-modified aptamer demonstrated its high binding affinity and specificity, and was able to distinguish white adipocytes from 3T3-L1 preadipocytes or brown adipocyte s in vitro. PS-modified Adipo8 also demonstrated more biostability and prolonged binding time in biological fluids. Additionally, Adipo8 could inhibit adipogenic differentiation of adipose tissue, possibly by the expression of PPAR-gamma in adipose tissue. This modified aptamer holds great promise as a stable molecular recognition tool for targeted delivery to adipocytes and has potential in the treatment of obesity.