The nanotechnology has an important role in improving the efficacy and safety in therapy. The present study explains the antifungal and the immunomodulatory potency of propolis nanoparticles (PNPs) against Fusarium solani in Albino Mice. Disc diffusion method was used for antifungal efficacy of PNPs. Moreover, PNPs exhibited a progressive decrease in the % of viable Vero cells and suppressed the virulence factors of Fusarium saloni including adhesion and biofilm formation. In animal experiments, lymphoid cell, peritoneal phagocytes, red blood cell RBCs and white blood cell WBCs counts and the activities of T and B-lymphocytes were determined. In addition, T-cell mitogenesis cells, serum level of interleukin 2 (IL-2) and haemoglobin Hb concentration were measured. PNPs exhibited high inhibition zone with most of Fusarium solani isolates. The results indicated that treatment of mice by PNPs showed a marked rise in the number of cells from thymus, spleen, mesenteric lymph nodes and bone marrow. Furthermore, PNPs caused statistically significant raised in Hb concentration and WBCs count. These results confirmed that many biological activities attributed to PNPs and is as an adjuvant for immune enhancement.