Aims New vaccines based on recombinant and DNA proteins are safer than traditional vaccines, but unfortunately, they have lower immunogenicity. Therefore, there is a need for the development of safe and strong adjuvants that can increase the immune response of the vaccine. Glycolic acid lactic polyester (PLGA), a copolymer ester, consists of acidic and polyglycolic lactic acid. Its hydrolysis leads to the production of lactic acid and glycolic acid monomers. The aim of this study was to compare humoral and cell mediated immune response to tetanustoxin coated PLGA in mice. Materials & Methods In this experimental study, PLGA nanoparticles were produced by water/oil (W/O) method. Tetanus toxin were covalently attached to nanoparticles by EDC. After coated nanoparticles characterization, they were injected into different groups of mice. The Freunds complete adjuvant and Alum were used as control. After a single injection, the immunostimulation of humoral immuneresponse was investigated by ELISA and cellular immunresponse eas analyzed by spleen cell proliferation assay. One-way analysis of variance was used. Findings PLGA nanoparticles had a strong adjuvant effect, and when used with antigens, could produce cellular and humoral immune response far more powerful than alum adjuvant and equall than Freund’ s adjuvant. Conclusion Glycolic acid lactic polyester, in the form of conjugation with an antigen, can be used to increase the immune response, especially in the cellular immune arm, relative to the antigenic solution. Although PLGA adjuvant seems not so successful to the humoral immune stimulus against alum adjuvant, but in comparison to the full adjuvant of Freunds, it can be a significant competitor with single injection.