Hymenolepis nana is the most commonly known intestinal cestode infecting mainly human. This study aimed to investigate the potential effect of chitosan particles (CSP) to enhance the immune system against H. nana infection. Determination of worm burden, egg output, histopathological changes, oxidative stress markers (lipid peroxidation and reduced glutathione), goblet (GCs) and mucosal mast cells (MMCs) counts in intestinal ileum was performed. In addition, levels of intestinal mRNA expression of interleukin (IL)-4, IL-9, stem cell factor (SCF), type I and II interferons (IFN)-α/ γ, tumour necrosis factor (TNF)-α, mucin 2 (MUC2) and inducible nitric oxide synthase (iNOs) were investigated using real-time PCR. The results indicated induced reductions in adult worm and egg counts in infected mice after CSP treatment. This was associated with improvement in tissue morphometric measurements and oxidative stress which were altered after infection. Expression levels of iNOs, IFN-α, IFN-γ, TNF-α and IL-9 were decreased by CSP. Conversely, expression levels of MUC2, IL-4 and SCF increased compared to infected untreated group. In addition, GCs and MMCs counts were normalized by CSP. In conclusion, this study could indicate the immunoprotective effect of CSP against H. nana infection. This was characterized with Th2 anti-inflammatory responses.