Immunosuppressive cells in the pancreatic cancer microenvironment play an important role in tumor development. Various immunosuppressive cytokines are secreted by these cells. Immunosuppressive cells may also influence the chemotherapeutic effect as well as promote drug resistance. Gemcitabine, albumin-bound paclitaxel, and other first-line chemotherapy agents not only suppress the proliferation of pancreatic cancer cells directly but also indirectly reinforce the anti-tumor effect of immune cells. However, chemo-therapeutic drugs may also induce immunosuppression, drug resistance, and tumor progression. In this review, we summarize the im-munosuppressive features of the pancreatic cancer microenvironment and its reciprocal relationship with chemotherapy, aiming to op-timize the current chemotherapy strategies from the perspective of the tumor immune microenvironment.