Abstract: Poly(D, L-lactide) (PDLLA) with high molecular weight was prepared by ring opening polymerization (ROP) of D, L-lactide. Effects of reaction temperature, reaction time and molar ratio of catalyst to monomer on the molecular weight of PDLLA were investigated through orthogonal synthesis experiments to optimize the polymerization parameters. The number-average molecular weight, chemical structure, thermal properties and mechanical properties of the prepared PDLLA were analyzed by gel chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), differential scanning calorimeter (DSC), thermogravimetric analysis (TGA) and universal testing instruments. The degradation properties and cytocompability against fibroblasts (L929) of PDLLA were also evaluated in vitro. The orthogonal experimental results indicated that the optimal parameters for synthesis of high molecular weight PDLLA were that with the molar ratio of catalyst to monomer of 2.04∶5 000, the reaction temperature at 135 °C, and the polymerization time for 4.5 h. Under such conditions, PDLLA with a number–average molecular weight of 2.01×10⁵ was obtained. When the monomer conversion rate was considered in the meantime, the reaction time could be selected as 6.0 h. The obtained PDLLA had a tensile strength of (39.91±1.34) MPa, an elongation at break of 3.94%±0.54%, and an elastic modulus of (1.68±0.34) GPa. The degradation rate increased rapidly after 220 d incubation in phosphate buffer saline (PBS). The PDLLA membrane could promote the proliferation of fibroblasts in vitro, indicating its good cytobiocompatability.