Objective:To investigate the expression of carbonic anhydrase Ⅱ(CAⅡ) in colorectal cancer(CRC), and the correlation with the carcinogenesis, development and clinical pathological aspects of CRC. Methods:CAⅡ was detected in paired fresh samples of 12 CRC and the mucosa distant to cancer (normal mucosa) with Western Blot. Then the expression of CAⅡ was detected in paired samples of 64 CRC and normal mucosa, 27 polyps, and 20 metastatic lymph nodes with immunohistochemistry. The differences among them were analyzed. The correlation of CAⅡ expression with the location, differentiation and clinical pathological stage of CRC was also analyzed. Results:Western Blot analysis showed that the intensity of CAⅡ/tubulin in normal mucosa and CRC was 2.48±1.68 and 1.33±1.28, respectively （P=0.027）.Immunohistochemistry analysis showed that the expression scores of CAⅡ in normal mucosa（2.81±0.48）, polyp(including hyperplasic polyp and adenoma, (2.56±0.51) and CRC（1.30±0.89） were stepwisely down-regulated significantly（P＜0.05）. However, the expression of CAⅡ in lymph node metastasis（1.35±0.67） was similar to its primary tumor（P＞0.05）. The expression of CAⅡin CRC had no significant difference among different cancer locations, differentiation or TNM stages（P＞0.05）. Conclusions:The down-regulation of CAⅡ is an early event of CRC carcinogenesis. It has no correlation with differentiation, TNM stage or metastasis.