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Low molecular weight heparins (LMWHs) are obtained from unfractionated heparin (UFH) through different depolymerization methods (DM), which produce compounds having specific chemical features and biological activity. It is then supposed that LMWHs also exhibit different skin permeability properties. The current work aimed to get an insight on the in vitro passive diffusion through human epidermis of six commercially available LMWHs in comparison with UFH. The in vitro studies were performed using Franz diffusion cells. Heparins samples were assayed measuring the anti-factor Xa activity. Circular dichroism was used to evaluate the effect of the counter-ion (sodium or calcium) on the chain flexibility. The penetrated amounts after 24 h (Q24) of sodium LMWHs were related to Mw by an exponential relationship (R = −0.758). The flux resulted dependent by DM following the rank order: β-elimination (8–11 mIU/cm2 h range) > deaminative cleavage (5–7 mIU/cm2 h range) > radical depolymerization (0.1 mIU/cm2 h). Finally, the calcium ion, reducing the chain flexibility, significantly affected the Q24 (0.001 ± 0.000 and 0.157 ± 0.049 IU/cm2 for calcium and sodium nadroparin, respectively). Both the lower Mw and the introduction of new residues at the chain ends improved the skin penetration of LMWHs with respect to UFH (Q24 = 0.001 ± 0.001 IU/cm2), with bemiparin and enoxaparin being the most interesting compounds.