〔Abstract〕 Objective To investigate the effect of insulin-like growth factor Ⅱ(IGF-Ⅱ) methylation on trophoblast cells apoptosis induced by high glucose and PI3 K/Akt pathway. Methods Human choriotrophoblast cell line HTR-8/SVneo was culturedin vitroand randomly divided into control group, high glucose group, 5-Aza-2′-deoxycytidine(methyltransferase inhibitor)+high glucose group(50 mmol/L of glucose). High glucose group and 5-aza-dc+high glucose group were cultured in high glucose medium, then 5-aza-dc+high glucose group was treated with 5-aza-dc. The methylation level of IGF-Ⅱ was detected by nested methylation specific PCR(nMS_PCR). The cell proliferation was detected by CKK-8. The cell apoptosis rate was detected by flow cytometry. The expressions of IGF-Ⅱ protein, apoptosis-related protein(Bcl-2, Bax, caspase-3), PI3 K/Akt pathway protein(PI3 K, p-PI3 K, Akt, p-Akt) were detected by Western blot. Results Compared with the control group, the cell relative survival rate and the expressions of IGF-Ⅱ, Bcl-2, p-PI3 K and p-Akt proteins in the high glucose group decreased(P<0.05); the methylation level of IGF-Ⅱ, apoptotic rate, expressions of Bax and caspase-3 protein increased(P<0.05), the expressions of PI3 K and Akt protein did not change(P>0.05). Compared with the high glucose group, the relative survival rate and the expressions of IGF-Ⅱ, Bcl-2, p-PI3 K and p-Akt in the 5-aza-dc+high glucose group increased(P<0.05); IGF-Ⅱ methylation level, apoptotic rate, Bax and caspase-3 protein expressions decreased(P<0.05), the expressions of PI3 K and Akt protein did not change(P>0.05). Conclusion IGF-Ⅱ methylation mediates trophoblast cells apoptosis induced by high glucose. Inhibition of IGF-Ⅱ methylation can promote proliferation and inhibit apoptosis of trophoblast cells, which may be achieved by up-regulating PI3 K/Akt pathway.