Background: Trichinellosis is a worldwide re-emerging parasitic disease, affecting humans. This study aimed to assess the efficacy of nitazoxanide (NTZ) loaded on solid lipid nanoparticles (SLNs) for the treatment of murine Trichinella spiralis infection in comparison with the crude nitazoxanide and ivermectin. Methods: 160 Male Swiss albino mice were divided into eight groups. Each group was further subdivided into the intestinal phase & muscular phase; G1: healthy not infected control, G2: infected control group, G3: infected and treated with SLNs, G4: infected and treated with ivermectin, G5: infected and treated with NTZ, G6: infected and treated with NTZ-SLNs, G7: infected and treated with ivermectin combined with NTZ and G8: infected then treated with ivermectin combined with NTZ-SLNs. All groups except G1 were orally infected with 250-300 T. spiralis larvae. Assessment of the treatment efficacy was performed parasitologically, histopathologically and serologically. Results: A significant reduction in the number of intestinal adult worm and encysted muscular larvae in all treated groups was found with highest reduction rate in G8 (99.1%,89%). These results were confirmed by histopathological improvement of the targeted groups. Conclusion: Although NTZ was inferior to ivermectin in the treatment of trichinellosis during the intestinal phase, it was superior to it in the muscular phase. Loading NTZ on SLNs resulted in increasing its efficacy against both intestinal and muscular phases. The combinations between ivermectin and the crude and loaded NTZ showed higher efficacies. ELISA results were non-significant, being not valid for the follow up of the treatment efficacy.