Platelet rich plasma (PRP), a cocktail of platelet growth factors and bio-active proteins, has been proposed as therapeutic agent to restore damaged articular cartilage. We report the biological effect of the platelet lysate (PL), a PRP derivative, on primary human articular chondrocytes cultured under both physiological and inflammatory condition. When added to the culture medium, PL induced a strong mitogenic response in the chondrocytes. The in vitro expanded cell population maintained a chondrogenic re-differentiation potential as revealed by micromass culture in vitro and ectopic cartilage formation in vivo. Furthermore, in chondrocytes cultured in the presence of the pro-inflammatory cytokine IL-1α, the PL induced a drastic enhancement of the synthesis of the cytokines IL-6 and IL-8 and of NGAL, a lipocalin expressed in cells of the chondrogenic lineage. These events were controlled by the p38 MAP kinase and NF-κΒ pathways. The pro-inflammatory effect of the PL was a transient phenomenon. In fact, after an initial up regulation, we observed a significant reduction of the NF-κΒ activity together with the repression of the inflammatory enzyme ciclooxygenase-2 (COX-2). Moreover, the medium of chondrocytes cultured in the contemporary presence of PL and IL-1α, showed a significant enhancement of the chemoattractant activity versus untreated chondrocytes. On the whole, our findings support the concept that the platelet products have a direct beneficial effect on articular chondrocytes and at the same time could drive in sequence a transient activation and the resolution of the inflammatory process, thus providing a rational for their use as therapeutic agents in cartilage inflammation and damage.