Endothelialisation of vascular substitutes, in fact, remains one of the most unsolved problems in cardiovascular diseases treatment. Stromal Derived Factor 1 (SDF-1) has been largely investigated as an endothelialisation promoter and Pleiotrophin is a promising alternative. Although it has been known to exert beneficial effects on different cell types, its potential as an inducer of proliferation and migration of endothelial cells was not investigated. Therefore, this work is aimed to compare the effects of Pleiotrophin on proliferation and migration of endothelial cells with respect to SDF-1.Endothelial cell line EA.hy926 was treated with Pleiotrophin (50 ng/ml) or SDF-1 (50 ng/ml). Cell viability was evaluated by MTT assay and migration assays were performed in Transwell chambers. Wound healing potential was evaluated by scratch wound assay. CXCR4, RPTP β/ζ, PCNA and Rac1 expression was detected by Western Blot.Interestingly, Pleiotrophin significantly increased the viability of the treated endothelial cells with respects to SDF-1. The migratory ability of the endothelial cells was also improved in the presence of Pleiotrophin with reference to the SDF-1 treatment. Moreover, Western Blot analysis showed how the treatment with Pleiotrophin can induce an increase in the expression of RPTP β/ζ, PCNA and Rac1 compared to SDF-1.Due to the significant effects exerted on viability, migration and repair ability of endothelial cells compared to SDF-1, Pleiotrophin can be considered as an interesting molecule to promote re-endothelialisation.