Objective Diabetes mellitus can cause spontaneous abortion, neonatal diseases, congenital malformations, and death. There are many studies related to the damage of in vitro hyperglycemia on embryogenesis in literature, but not enough studies on in vivo hyperglycemia effects on embryogenesis. Fibroblast growth factor (FGF) molecules play an essential role in pre-implantation embryo development and diabetes pathogenesis. In our study, we researched whether FGF-4 and FGFR-2 were playing a role in maternal diabetes' effects on embryo development. Material and Methods Thirty adult virgin female BALB/c mice were randomly divided into two groups: control and diabetic. The experimental diabetes model was generated by streptozotocin (55 mg/kg, once, intraperitoneally). The control and the diabetic group were mated. Embryos were collected at the morula and blastocyte stages corresponding to the third and fourth days of pregnancy. Embryo's FGF-4 and FGFR-2 molecules were evaluated by their immunofluorescence staining and immunoreactivity score. Result The results clearly showed that the FGF-4 and FGFR-2 immunofluorescence reactivity was higher in the diabetes group. Conclusion We concluded that FGF-4 and FGFR-2 overexpression might impair mouse pre-implantation embryo development in maternal diabetes and suggest investigating whether they have crucial effects on human embryo development and infertility in maternal diabetes.