Case 1: A 58-year-old man who initially presented with diarrhea was diagnosed with rectal gastrointestinal stromal tumor (GIST). The patient initially received neoadjuvant therapy with imatinib mesylate. After imatinib therapy( 400 mg/day) for 23 weeks, the patient's abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scans showed a reduction of approximately 67% in tumor size. He underwent sphincter-preserving surgery with intersphincteric resection, and the tumor was resected radically and safely. Case 2: A 66-year-old man with a complaint of hematochezia was diagnosed with rectal GIST during treatment for infective endocarditis. Neoadjuvant imatinib therapy (400 mg/day) was started. However, the treatment was stopped after 11 weeks because of rhabdomyolysis, which was suspected to be an adverse effect of imatinib administration. Abdominal CT and MRI revealed a reduction of approximately 53% in tumor size. A radical operation was considered feasible and sphincter-preserving surgery with intersphincteric resection was performed. Currently, neoadjuvant imatinib mesylate therapy is performed in the setting of clinical trials, but the cases suggest that it can be a promising strategy for locally advanced rectal GIST, improving the complete resection rate and the safety of operations by reducing the size of the tumor.