Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The mechanism for most GIST is considered to be the gain-of-function mutations of the c-Kit gene and Kit protein expression which cause the sustained activation of its down-stream signaling pathways and thereby the continuous proliferation of the tumor cells. As a tyrosine kinase inhibitor, application of imatinib has allowed the targeted therapy to become an important therapeutic option besides surgical treatment for GIST, and significantly influenced the treatment mode of GIST. Foxp3+Treg cells are important regulatory T population, and they negatively control the anti-tumor immune responses through suppressing the anti-tumor cells such as CTL and NK cells. Studies have revealed that imatinib inhibits GIST through not only targeted mechanism but also immunological mechanisms by suppressing the Foxp3+Treg cells and enhancing the anti-tumor immune responses. Here, the authors present research progress of the effects of imatinib on the peripheral blood Foxp3+Treg cells and their subpopulations in patients with GIST.