P38 conveys a variety of signals, including conventional growth, migratory and death signals, as well as responding to environmental and mechanical stimuli. These signals induce phosphorylation of p38, which triggers both its translocation to the nucleus and the activation of its catalytic function. In Paracentrotus lividus we have shown that for a correct cilia re-generation the p38 activation is essential; we also showed, by time course Western blotting, two activation peaks during development (morula and early gastrula stages) with a precise localization of activated p38 in micromere and micromere derived cells (Nichel treatment higlighted this feature), and in the oral apical region. These results suggest that, like in Lytechinus variegatus, p38 activation/inactivation is involved in O-A axis specification, in gastrulation and in skeletogenesis. We found, in fact, that inhibiting (with SB203580) the p38 activation during cleavage (up to the morula stage) anomalies were observed in gastrulation (exogastrulae); later inhibition treatment (morula/blastula transition) impaired skeleton formation. Finally we was also able to demonstrate that in P. lividus are present four p38 isoforms differentially involved in different stress responses. All these features driven us to analyze if p38 activation is involved in high density population response in the “Ustica Island” MPA.