The effects of thalidomide after intraperitoneal instillation on the healing of colonic anastomoses are not known. A series of 40 New Zealand White rabbits underwent an end-to-end colonic anastomosis. The animals were randomized into four groups. Groups 1 (n = 10) and 2 (n = 10) were treated with dissolved thalidomide 200 mg/kg intraperitoneally, whereas groups 3 (n = 10) and 4 (n = 10) were treated only with the dissolver. Animals were sacrificed at day 3 (groups 1, 3) and day 7 (groups 2, 4). Anastomotic healing was tested by measuring the bursting pressure in vitro. Immunohistochemical staining of the anastomotic site was performed with polyclonal antibodies against CD31 and Mib-1, to determine a possible antiangiogenic or antiproliferative effect. Statistical analysis was performed using Spearman's log rank correlation and paired t-test. On postoperative day 3 (p > 0.19) and postoperative day 7 (p > 0.73), there was no difference in bursting pressure in the treatment and the control groups. Angiogenesis scores were reduced at day 3 in the thalidomide group (p < 0.05), but did not differ between the groups at day 7. White blood cell counts were decreased in the treatment groups at day 3 (p < 0.01) and day 7, compared to control groups (p < 0.01). There was no difference in the expression of Mib-1 in either group at day 3 or day 7. The intraperitoneal administration of thalidomide does not interfere with the healing of colonic anastomosis. Although the angiogenesis score is diminished at day 3, this did not lead to a reduced bursting pressure at day 3 or day 7.