To investigate the influence of initial copolymer compositions of poly (lactic-co-glycolic acid) (PLGA) on mechanical properties, degradation behavior and biological properties of the scaffolds, porous PLGA scaffolds with different initial copolymer compositions (lactide/glycolide (PLA/PGA) molar ratio: 50:50, 70:30 and 80:20) were prepared by solvent casting/particulate leaching method. Mechanical properties were measured by testing the tensile strength and degradation rate was detected by soaking the scaffolds in phosphate buffered solution at 37 °C for various time points. Human dermal fibroblasts were seeded on PLGA scaffolds with different copolymer compositions. The morphology, adhesion efficiency, proliferation rate, and total collagen contents of cells on the scaffolds were analyzed. The results showed that the ratio of PLA/PGA is one important factor which influences the degradation of scaffolds. The mechanical strength of PLGA scaffolds with the ratio of 70:30 and 80:20, was higher than that of PLGA scaffolds with the ratio of 50:50.. Compared to 70:30 and 80:20 PLGA scaffolds, 50:50 PLGA had a quicker degradation. The three PLGA scaffolds had no obvious difference for cell response and all of them had excellent cytocompatibility, indicated by their high efficiency for human dermal fibroblast adhesion, fast proliferation rate and stretched cell morphology. A large amount of extracellular matrix was secreted and after 7 days of culture, and cell nearly covered the entire surface of the scaffolds. Overall, our results indicate that the copolymer compositions of PLGA have important effect on degradation and mechanical strength, but have no obvious effect on the biological properties of the scaffolds.