The axolotl (Ambystoma mexicanum) salamander, a urodele amphibian, has an exceptional regenerative capacity to fully restore an amputated limb throughout the life-long lasting neoteny. By contrast, when axolotls are experimentally induced to metamorphosis, attenuation of the limb’s regenerative competence is noticeable. Here, we sought to discern the proteomic profiles of the early stages of blastema formation of neotenic and metamorphic axolotls after limb amputation by employing LC-MS/MS technology. We quantified a total of 714 proteins and qRT-PCR for selected genes was performed to validate the proteomics results and provide evidence for the putative link between immune system activity and regenerative potential. This study provides new insights for examination of common and distinct molecular mechanisms in regeneration-permissive neotenic and regeneration-deficient metamorphic stages at the proteome level.