Objective To detect expressions of CD31 and D2-40 in patients with simultaneous colorectal cancer with peritoneal metastasis and investigate their correlation between them. Method The expressions of CD31 and D2-40 protein in these 59 cases (there were 19 and 40 patients with or without peritoneal metastasis, respectively) of colorectal cancer were detected by immunohistochemical MaxVision method. Results ① The positive rates of CD31 and D2-40 protein expression in the colorectal cancer tissues with or without peritoneal metastasis were significantly higher than those of the normal colonic tissues (P<0.05), but which had no significant differences between the colorectal cancer tissues with or without peritoneal metastasis (P>0.05). ② The CD31 microvessel density (CD31-MVD) and D2-40 lymphatic microvessel density (D2-40-LMVD) in the colorectal cancer tissues with peritoneal metastasis were significantly higher than those of the normal colonic tissues (P<0.05) and the colorectal cancer tissues without peritoneal metastasis (P<0.05). ③ The CD31-MVD and D2-40-LMVD were not associated with all the clinicopathologic characteristics of the colorectal cancer patients without peritoneal metastasis (P>0.05), but which in the poorly differentiated adenocarcinoma and mucinous and signet ring cell carcinomas patients with peritoneal metastasis were significantly higher than those of the other types (P<0.05) and were not associated with the age, gender, and diamter of the tumor of it (P>0.05). ④ There was a positive correlation between the CD31-MVD and the D2-40-LMVD in the colorectal cancer patients with or without peritoneal metastasis (r=0.342, P=0.012; r=0.119, P=0.008). Conclusions CD31-MVD and D2-40-LMVD in colorectal cancer patients with peritoneal metastasis highly express and has a positive correlation, which means that they might have a certain relationship with peritoneal metastasis. There may be some common regulation way and collaboratively participate peritoneal metastasis of colorectal cancer.