Objective To establish a nude mouse model of low rectal cancer with lymph node metastasis, to detect the expression of E-calcium (E-cad) in the serum and transplanted tumor tissue of the mice, and to analyze the role of E-cad in lymph node metastasis of rectal cancer. Methods Human colorectal adenocarcinoma cells (SW-480) were inoculated into the rectal submucosa of nude mice to establish a model of low rectal cancer with lymph node metastasis. 120 nude mice were randomly divided into three groups (40 mice in each group). Group A (rectal cancer model group) was injected with dimethylhydrazine and implanted with SW480 cells. Group B (dimethylhydrazine control group) was injected with dimethylhydrazine alone. The group C (control group) received no treatment. Serum E-cad was detected by ELISA. The mRNA and protein expression of E-cad in the tumor tissue was detected by RT-PCR and western blot, respectively. Results The serum level of E-cad in group A was 19.48±1.25 mg/L, significantly higher than those in groups B (2.36±0.18 mg/L) and C (2.15±0.12 mg/L) (t=8.28, 9.01, P< 0.05). The serum levels of E-cad were significantly higher in the nude mice with lateral lymph node metastasis than those without lymph node metastasis (t=10.28, P< 0.05). The protein expression of E-cad in the group A was lower than that in the groups B and C (t=9.81, 7.69, P< 0.05). In the group A, the protein expression of E-cad in the nude mice with lateral lymph node metastasis was significantly lower than that without lateral lymph node metastasis (t=9.36, P< 0.05). The mRNA expression of E-cad in the group A was significantly lower than that in the groups B and C (P< 0.05), and the mRNA expression of E-cad in the nude mice with lateral lymph node metastasis was significantly lower than that in the mice without lateral lymph node metastasis (t=7.85, P< 0.05). Conclusions The serum level of E-cad may be closely associated with the lymphatic metastasis of rectal cancer, and the mRNA and protein expressions of E-cad in colorectal cancer tissue were weak or absent, leading to a decrease of adhesion ability between cancer cells, and promote the invasion and metastasis of cancer cells.