Mammalian target of rapamycin (mTOR) has recently emerged as a promising target for the treatment of several human cancer types. Rapamycin, a classical mTOR inhibitor, has been shown to be effective as an antitumour therapy in a variety of preclinical trials. However, the clinical use of rapamycin has been limited by its poor water solubility, low bioavailability, and instability in circulation. In this manuscript, we described the preparation of rapamycin-loaded glucan particle (GP)/chitosan (CS)/tripolyphosphate (TPP)/alginate (ALG) microparticles (GP-rapamycin microparticles) by ionotropic gelation and evaluated its loading and encapsulation efficiency. The prepared GP-rapamycin microparticles displayed excellent stability, sustained release properties, and low toxicity. In addition, the new delivery system effectively inhibited the growth of melanoma, enhanced the number of apoptotic tumour cells, upregulated the percentage of inflammatory monocytes (CD11b+ Ly6C+) in the spleen, and increased the infiltration of CD3+ T cells in tumour tissue. Collectively, this study reveals a new platform for drug delivery and expands the understanding of GP drug loading to enhance the antitumour immune response.