KIR2DL4 is an interesting receptor expressed on the peripheral blood natural killer (pbNK) cell as it can be either activating or inhibitory depending on the amino acid residues in the domain. This model uses mathematical modelling to investigate the downstream effects of natural killer cells’ activation (KIR2DL4) receptor after stimulation by key ligand (HLA-G) on pbNK cells. Development of this large pathway is based on a comprehensive qualitative description of pbNKs’ intracellular signalling pathways leading to chemokine and cytotoxin secretion, obtained from the KEGG database (https://www.genome.jp/kegg-bin/show pathway?hsa04650). From this qualitative description we built a quantitative model for the pathway, reusing existing curated models where possible and implementing new models as needed. This large pathway consists of two published sub-models; the Ca2+ model and the NFAT model, and a newly built FCeRIγ sub-model. The full pathway was fitted to HLA-G-KIR2DL4 pathway published dataset and the model that we developed fitted well to one of two secreted cytokines. The model can be used to predict the production of IFNγ and TNFα cytokines.