AIM: To study the expression and the role of ERK1/2 and JNK1/2 of MAPKs pathways in the development of neural tube defects induced by hyperthermia. METHODS: The animal models of golden hamster were produced by hyperthermia. The expression of ERK1/2 and JNK1/2, and levels of their phosphorylation were measured by Western blotting in control group and hyperthermia group. RESULTS: p-ERK1/2 steadily expressed in each control group, and the expression of p-ERK1/2 significantly decreased, which was different from that in the corresponding control group (P<0.05). The activity of p-JNK1/2 increased in hyperthermia group and the amount of p-JNK1/2 increased as compared to control group. The peak appeared at 16 h after exposed to hyperthermia (P<0.05). CONCLUSION: Hyperthermia, which induces a decrease in p-ERK1/2 expression and increases the expression of p-JNK1/2 of MAPKs pathway, results in the unbalance of cell proliferation and apoptosis, and induces neural tube defects.