The axolotl is a highly regenerative species, capable of restoring full limbs, regardless of theamputation site. However, the regeneration rate is adjusted with the plane of amputation alongthe proximo-distal (PD) axis, leading to equivalent regeneration times regardless of the extentof tissue removal. We hypothesized that this phenomenon could be partly explained bydifferences in tissue mechanical properties. In this work, we describe tissue growthmathematically and evaluate cell cycle parameters of regenerating limbs amputated atdifferent levels along the PD axis, demonstrating a linear correlation between the cell cyclelength and the amputation site during early regeneration phases. We show as well, thatblastema cells require their endogenous context to retain such proliferation differences. Wemeasured mechanical properties in regenerating limbs with in vivo optical and standardindentation-based techniques and demonstrated that distal blastema cells are stiffer thanproximal ones. Accordingly, we demonstrated that axolotl cells decrease their proliferation withincreased extracellular matrix stiffness in vitro. Next, we evaluated the activity of themechanotransducers YAP/TAZ in vivo by using a GTIIC-based reporter line combined withtarget gene expression data, which indicated that their activity peaks during the blastemastage, with higher activity after proximal amputations. Hence, our findings strongly suggest amechanical dependence for the position-dependent regulation of cell proliferation duringaxolotl limb regeneration, where YAP/TAZ likely plays a role in the mechanotransductionmechanism.