Equine platelet lysate (ePL) is an acellular platelet derivative that is rich in growth factors and can be manufactured from platelet concentrate. Recently, ePL has been proven to decrease TNF- production, a pro-inflammatory cytokine, from stimulated monocytes. EPL optimization was explored in order to further modulate monocyte cytokine production. Fibrinogen and immunoglobulin depletion methods from ePL were investigated since they have the potential to initiate an inflammatory response. The depletion method that preserved the most growth factors was used for subsequent leukocyte assays. Monocytes and neutrophils were cultured with fibrinogen depleted platelet lysate (fdePL) to measure cytokine production, and phagocytosis/ROS production, respectively. Although fdePL did not further suppress TNF- production, there was significant enhancement in neutrophil phagocytosis and ROS production compared to ePL. In conclusion, fdePL comparably suppresses TNF-, and modulates neutrophil inflammatory reaction.