ABSTRACT: Platelet-rich fibrin (PRF) is prepared from the coagulated plasma of fractionated blood. When squeezing between two plates, PRF is separated into the solid PRF membranes and a liquid exudate, the PRF serum. The question arises regarding the extent to which the overall PRF activity remains in the membranes and what is lost in the serum. To this aim, we have exposed gingival fibroblasts to lysates prepared from PRF membranes and PRF serum, followed by bulk RNA sequencing. A total of 268 up- and 136 down-regulated genes in gingival fibroblasts exposed to PRF lysates are significantly regulated under the premise of a minimum log2 2.5-fold change and a minus log10 significance level of two, respectively. PRF serum caused 62 up- and 32 down-regulated genes when gingival fibroblasts were exposed to PRF serum, respectively. Among the 61 genes commonly up-regulated by PRF lysate and serum were CXCL1, CXCL5, CXCL6, CXCL8, IL33, and IL6 and PTGS2, STC1. PRF lysate further increased the chemokines CCL2, CCL7, CXCL2, CXCL3, and the IL1R1, IL1RL1, and IL1RN – as well as the paracrine factors IL11, LIF, IGF1, BMP2, BMP6, FGF2, CCN2/CTGF and HAS1, HAS2, HAS3. The 16 up-regulated genes by PRF serum included DKK1. Among the 122 down-regulated genes by PRF lysate were IFIT1, IFIT2, IFIT3, OSR1, OSR2. Among the 32 down-regulated genes by PRF serum were FGF18 and GDF15. Taken together, PRF lysates, compared to PRF serum, cause a more complex response of gingival fibroblasts with a chemokine with an obvious increase in chemokine expression and spectrum of paracrine factors.