Abstract: Objective To evaluate the antitumor activity and toxicity of chemotherapy plus rh-endostatin(endastar) and thalidomide for metastatic colorectal cancer. Methods Forty-seven patients with histologically or pathologically documented metastatic colorectal cancer who underwent endostar and thalidomide-based chemotherapy from January 2006 to January 2013 in our hospital were included in this study. Response to chemotherapy was assessed by RECIST criteria 1.0 and toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria（NCI-CTC） 4.0. The above patients were followed up. Endostar was administered biweekly by intravenous infusion at a dose of 15 mg per day， d1~d10. Thalidomide was administered orally at a dose of 150/200 mg qn， d1~d10. The combined chemotherapy regimens included oxaliplatin and fluoropyrimidine（18 cases）， oxaliplatin and raltitrexed（1 case）， irinotecan and fluoropyrimidine（26 cases） and irinotecan and raltitrexed（2 cases）. Results The median overall survival in first， second and third-line setting were 26.1 months（95%CI： 21.9-30.2）， 15.3 months（95%CI： 9.5-21.0） and 7.5 months（95%CI： 4.2-10.7）， respectively. The median progression-free survival in first， second， and third-line setting were 12.1 months（95%CI： 8.6-13.7）， 7.9 months（95%CI： 4.7-11.2） and 4.2 months（95%CI： 1.5-7.0）， respectively. The overall response rates in first， second and third-line setting were 63.1%， 37.5% and 16.7%， respectively. The disease control rates in first， second and third-line were 84.2%， 68.7% and 66.7%， respectively. The main adverse reaction included leukopenia， neutropenia， anemia， nausea and vomiting， mainly in grade 1-2. The most commonly encountered grade 3 to 4 adverse events included neutropenia（8.5%）， thrombocytopenia（6.4%）， nausea（4.3%）， vomiting（4.3%）， constipation（4.3%）， fatigue（2.1%） and peripheral neuropathy（2.1%）. Conclusion Endostar and thalidomide plus chemotherapy have antitumor activity and are well-tolerated in patients with metastatic colorectal cancer.