Angiostrongylus cantonensis infection can lead to severe neuropathological damage caused by the development of these nematodes in the central nervous system after penetrating the blood–brain barrier. They commonly cause eosinophilic meningitis or meningoencephalitis in non-permissive hosts (e.g., mice). It has been shown that differences exist in the brains of permissive and non-permissive hosts during the larval development of A. cantonensis; however, the mechanism underlying the difference is not completely understood. This study analyzed and characterized the differentially expressed proteins in the intracranial A. cantonensis larvae in rat (ILR) and mouse (ILM) brains by using proteomics. We found that 29 proteins were differentially expressed: 12 of these proteins were highly expressed in ILR, whereas the remaining 17 proteins were highly expressed in ILM. Three protein spots were homologous to the actin-2, actin-1, and disorganized muscle protein 1 (dim-1) of Caenorhabditis elegans. In addition, proteomic analyses revealed that act-1 and act-2 were up-regulated in ILM compared to ILR, whereas dim-1 was down-regulated in ILM. Annotation using gene ontology revealed that act-1, act-2, and dim-1 were mainly associated with adenosine triphosphate (ATP) catabolic processes and ATP binding. Quantitative real-time polymerase chain reaction analyses of act-1 and dim-1 using the first internal transcribed spacers of A. cantonensis 18S ribosomal RNA (rRNA) was consistent with 2-dimensional gel electrophoresis (2-DE) and the sizes of these parasites; ILR was longer and wider than ILM. These results indicate that the differentially expressed proteins dim-1 and act-1 could be related to the development and pathogenicity of A. cantonensis in different hosts.