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Objective: To investigate whether murine peroxidase reductase-5 (mPRDX5) has anti-tumor activity in mice, so as to further confirm the anti-tumor activity and mechanism of recombinant peroxidase reductase-5. Methods: High purity mPRDX5 was obtained by heterologous expression and purification in vitro. Pancreatic cancer Pan02 cells were inoculated subcutaneously on the left axillary back of mice to establish a tumor bearing mouse model. Mice were randomly divided into PBS (solvent control) group, GEM (gemcitabine) 50.0 mg/kg group and mPRDX5 10.0 mg/kg group, with 10 mice in each group, and the tumor related indexes were detected in mice. Results: Compared with PBS group, weight of tumor-bearing mice in GEM group was decreased obviously, while weight of mPRDX5 group was increased to a certain extent. Tumor growth was good in PBS group, according to tumor volume, compared with PBS group, tumor growth inhibition rates in D7 were 87.07% in GEM group and 52.82% in mPRDX5 10.0 mg/kg group, respectively ; according to tumor weight, compared with PBS group, GEM group and mPRDX5 10.0 mg/kg group had tumor growth inhibition rates of 95.39% and 48.33% in D7, respectively. Polarization state of macrophages in tumor tissues of mice in PBS group and mPRDX5 group was analyzed, and it was found that compared with PBS group, M1 macrophages expressing CD86 in tumor tissues of mice in mPRDX5 group were significantly increased, while M2 macrophages expressing CD206 were significantly decreased. Conclusion: mPRDX5 has significant anti-pancreatic cancer activity in mice, and the activity is exerted by promoting M1 -type polarization of macrophages in the tumor microenvironment. [ABSTRACT FROM AUTHOR]