Objective To study the expressions of caudal type homeodomain transcription factors CDX1 and CDX2 in different subtype of intestinal metaplasia (IM) and gastric eareinoma,and investigate their roles in the development and progression of IM and gastric carcinogenesis, and determine the relationship between IM and gastric carcinoma. Methods Forty eases of chronic superficial gastritis, 40 cases of chronic atrophic gastritis (CAG), 46 eases of CAG with IM, 40 cases of gastric carcinoma, and 32 eases of IM foci in para-eancerous tissues were selected respectively to construct tissue microarrays. Immunohistechemistry and in situ hybridization were used to assess the expressions of CDX2 protein and CDX1, CDX2 mRNA in different gastric lesions respectively. Results The proportion of type Ⅲ IM in IM foci in para-caucerous tissues was significantly higher than that in CAG (56.25% vs 21.74% ,P< 0.01). There was no expression of CDX1, CDX2 mRNA and CDX2 protein in chronic superficial gastritis and CAG without IM. The expression of CDX2 protein and CDX2 mRNA in CAG with IM, para-cancerous tissues and gastric carcinoma was 69.57%, 53.12%,42.50% (CDX2 protein) and 63.04%,46.88%,35.00% (CDX2 mRNA), respectively. The exprossions of CDX1 mRNA in above throe gastric lesions were 67.39%, 50.00%, 40.00%, respectively. The expressions of CDX2 protein and CDX2, CDX1 mRNA in gastric carcinoma were significantly lower than those in CAG with IM (P< 0.01). But there was no significant difference between gastric carcinoma and IM foci in para-cancerous tissues (P> 0.05). Furthermoro,the expressions of CDX2 protein were significantly associated with histological type of gastric carcinoma, which in intestinal-type was significantly higher than those in diffuse-type(54.55% vs 27.78%, P< 0.05). The expression of CDX2 protein in type Ⅲ IM was also significantly lower than that in type Ⅰ IM(46.43% vs 79.31%,P< 0.05). Conclusions CDX1 and CDX2 may play important roles in the development and progression of IM and gastric carcinoma, and may be new gastric carcinoma associated genes. Type Ⅲ IM is a precancerous lesion of the intestinal-type gastric carcinoma.