Objective: To assess the efficacy and safety of neoadjuvant imatinib therapy followed by transanal endoscopic microsurgery (TEM) for local excision of gastrointestinal stromal tumor (GIST) of the rectum. Methods: A group of thirteen patients with rectal GIST received imatinib therapy for 30-90 d and, after tumor regression, underwent TEM local excision of the tumor. The preoperative clinicopathologic profiles, response to neoadjuvant therapy, and relevant surgical variables of the patients were analyzed. Results: Remission was achieved in all patients within 3 months of neoadjuvant imatinib therapy, and significant tumor down-staging was seen. All patients, except one case that was converted to laparoscopic local rectal excision, received TEM local excision, of which 9 cases (70%) received operation after less than 2 months of neoadjuvant imatinib therapy. The average operative time was 45 min, and length of postoperative hospital stay was 6.7 d. The intraoperative blood loss in 11 patients (85%) was less than 20 mL, and no severe postoperative blood loss or infection occurred in any of the patients. No treatment-related death or other severe adverse reaction occurred. During follow-up, no recurrence or death occurred in the 12 patients undergoing TEM local excision. Conclusion: For some cases with locally progressive rectal GIST, preoperative imatinib therapy followed by TEM treatment can achieve favorable outcomes with high safety and minimal trauma, so it can be considered as a treatment option.